bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling variability of solar activity cycles
Authors: Kitchatinov L. L. , Mordvinov A. V. , Nepomnyashchikh A. A. 
Published: July 2018

Context. Solar activity cycles vary in amplitude and duration. The variations can be at least partly explained by fluctuations in dynamo parameters.
Aims. We want to restrict uncertainty in fluctuating dynamo parameters and find out which properties of the fluctuations control the amplitudes of the magnetic field and energy in variable dynamo cycles.
Methods. A flux-transport model for the solar dynamo with fluctuations of the Babcock–Leighton type α-effect was applied to generate statistics of magnetic cycles for our purposes. The statistics were compared with data on solar cycle periods to restrict the correlation time of dynamo fluctuations.
Results. A characteristic time of fluctuations in the α-effect is estimated to be close to the solar rotation period. The fluctuations produce asymmetry between the times of rise and descent of dynamo cycles, the rise time being on average shorter. The affect of the fluctuations on cycle amplitudes depends on the phase of the cycle in which the fluctuations occur. Negative fluctuations (decrease in α) in the rise phase delay decay of poloidal field and increase the cycle amplitude in toroidal field and magnetic energy. Negative fluctuation in the decline phase reduces the polar field at the end of a cycle and the amplitude of the next cycle. The low amplitude of the 24th solar cycle compared to the preceding 23rd cycle can be explained by this effect. Positive fluctuations in the descent phase enhance the magnetic energy of the next cycle by increasing the seed poloidal field for the next cycle. The statistics of the computed energies of the cycles suggest that superflares of ≥1034 erg are not possible on the Sun.
The TROY project
Authors: Lillo-Box J. , Leleu A. , Parviainen H. , Figueira P. , Mallonn M. , Correia A. C. M. , Santos N. C. , Robutel P. , Lendl M. , Boffin H. M. J. , Faria J. P. , Barrado D. , Neal J. 
Published: July 2018

Context.Co-orbital bodies are the byproduct of planet formation and evolution, as we know from the solar system. Although planet-size co-orbitals do not exists in our planetary system, dynamical studies show that they can remain stable for long periods of time in the gravitational well of massive planets. Should they exist, their detection is feasible with the current instrumentation.Aims.In this paper, we present new ground-based observations searching for these bodies co-orbiting with nine close-in (P< 5 days) planets, using various observing techniques. The combination of all of these techniques allows us to restrict the parameter space of any possible trojan in the system.Methods.We used multi-technique observations, comprised of radial velocity, precision photometry, and transit timing variations, both newly acquired in the context of the TROY project and publicly available, to constrain the presence of planet-size trojans in the Lagrangian points of nine known exoplanets.Results.We find no clear evidence of trojans in these nine systems through any of the techniques used down to the precision of the observations. However, this allows us to constrain the presence of any potential trojan in the system, especially in the trojan mass or radius vs. libration amplitude plane. In particular, we can set upper mass limits in the super-Earth mass regime for six of the studied systems.
Aktuelle Therapiestudien im Bereich der atypischen Parkinson Syndrome
Authors: Schweyer Kerstin , Levin Johannes , Höglinger Günter U. 
Published: July 2018

ZusammenfassungBei den atypischen Parkinson Syndromen handelt es sich um eine Gruppe neurodegenerativer Erkrankungen, die klinisch durch eine akinetisch-rigide Symptomatik mit zusätzlichen nicht-motorischen Symptomen gekennzeichnet sind. Anhand ihrer Pathologie, dem zugrundeliegenden fehlgefalteten Protein, lassen sich diese in Synucleinopathien (Multisystematrophie und Demenz vom Lewy-Body-Typ) und Tauopathien (progressive supranukleäre Blickparese und Kortikobasale Degeneration) einteilen. Dabei existieren bisher keine kausalen Therapiemöglichkeiten, in den meist rasch progredienten Krankheitsverlauf einzugreifen. Symptomatische Therapien besitzen nur einen kurzfristigen, häufig unbefriedigenden Effekt. In den letzten Jahren konnten durch präklinische Forschung Pathomechanismen in der Krankheitsentstehung charakterisiert werden. Dabei wurden Substanzen entwickelt, die beispielsweise die pathologische Protein-Aggregation oder in die Verbreitung der Pathologie verhindern und im Tiermodell einen Einfluss auf das Fortschreiten der Krankheit zeigen konnten. Dabei wurden erste klinische Studien, welche in die Entstehung der zugrundeliegenden Pathologie eingreifen, durchgeführt; viele befinden sich aktuell in der Rekrutierung oder Planung. In folgendem Artikel stellen wir die aktuellen Entwicklungen im Gebiet der atypischen Parkinson Syndrome vor und präsentieren die aktuellen Studien.
Evaluation of Organisational Structures of Self-help Groups in the Field of Paediatric Orthopaedics
Authors: Peterlein Christian-Dominik , Friedrich Sinja , Daniel Hanna , Malcherczyk Dominik , Ruden Janine , El Zayat Bilal 
Published: July 2018

Zusammenfassung
Hintergrund Studien über Selbsthilfegruppen zu Krankheitsbildern auf kinderorthopädischem Fachgebiet und deren Organisationsformen liegen im deutschsprachigen und internationalen Raum bisher noch nicht vor.
Material und Methoden Mittels eines auf postalischem Weg verschickten, standardisierten Fragebogens wurden gezielt Organisationsstruktur, Kommunikationsplattformen und Art der Finanzierung von dem Anforderungsprofil entsprechenden Selbsthilfegruppen ermittelt.
Ergebnisse Die zahlenmäßig häufigsten Rückmeldungen kamen von Selbsthilfegruppen zum Krankheitsbild Kleinwuchs, infantile Zerebralparese und Trisomie 21. Die Mehrzahl der befragten Selbsthilfegruppen hatte den Status eines eingetragenen Vereins und war einem Dachverband angeschlossen. Das Gründungsjahr war primär in der Dekade 1990 – 2000 (n = 15); Gründer waren überwiegend Eltern (n = 28; 77,8%), Betroffene (n = 11; 30,6%) und nur in 2 Fällen (5,6%) Ärzte. 80,6% der ausgewerteten Selbsthilfegruppen (n = 29) finanzierte sich auch über Spenden. Die Darstellung der Ziele, der Aktivitäten und der Möglichkeit einer ersten Kontaktaufnahme erfolgt primär über die eigene Homepage (n = 35; 97,2%). Nicht wenige Selbsthilfegruppen zu kinderorthopädischen Grunderkrankungen arbeiten mit Ärzten unterschiedlicher Disziplinen zusammen und lassen sich von diesen beraten.
Schlussfolgerung Diese Studie liefert erste Daten über Organisationsstrukturen kinderorthopädischer Selbsthilfegruppen und verdeutlicht die Interdisziplinarität des Fachs Kinderorthopädie. Eine enge Zusammenarbeit zwischen Kinderorthopäden und lokalen Selbsthilfegruppen könnte helfen, Ängste und Unsicherheiten abzubauen und die Qualität der medizinischen Versorgung vor Ort zu verbessern.
Prediction of Human Pharmacokinetics of Bendamustine from Preclinical Species Pharmacokinetics Based on Normalizing Time Course Profiles
Authors: Srinivas Nuggehally , Jairam Ravi , Mallurwar Sadanand , Sulochana Suresh , Chandrasekar Devaraj , Bhamidipati Ravi , Richter Wolfgang , Mullangi Ramesh 
Published: July 2018

AbstractBendamustine, an alkylating anticancer agent, is used to treat chronic lymphocytic leukemia by intravenous infusion alone or in combination. The work aimed to develop a method to predict time vs. concentration profile for humans based on preclinical pharmacokinetics using the assumption of superimposability of normalized time course profiles of animals and humans. Standard allometric equations with/without correction factors (CF) were also used in prediction. The Vss was predicted by simple allometry of 0.312W0.871 (r2=0.987), where W is body weight; predicted Vss (19.71 L) was similar to the reported value (20.10 L). However, CL prediction involved both simple and CF allometry. Best proximity CL (543 vs. 598 mL/min) was obtained with maximum life span correction (MLP) [2.46W1.215 (r2=0.988)]. Normalized curves were obtained by normalizing the time (with mean residence time) vs. concentration (with dose/Vss) in animal species. The concentration vs. time profile in humans after intravenous infusion was then simulated using normalized curve for each animal species and the values of CL and Vss were predicted for humans. In summary the findings indicate that normalized time course approach could predict the bendamustine human pharmacokinetics and such an approach could be prospectively applied for analog drugs of this class.
First Case of Sporadic Protein S Deficiency due to a Novel Candidate Mutation, Ala 484 → Pro, in the Protein S Active Gene (PROSl)
Authors: Borgel D , Jude B , Alach M , Gandrille S 
Published: July 2018

SummaryIn a series of 16 propositi with symptomatic protein S deficiency and a protein S gene mutation, we identified a sporadic case of a novel mutation that probably affects gene expression. The mutation, a G to C transversion leading to the substitution of Ala 484 by Pro, was not found in the protein S gene of the patient’s parents. Transmission of the paternal and maternal protein S alleles was apparently normal, on the basis of the frequent polymorphism in exon XV. We also checked the transmission of chromosomal material by analysing protein C gene polymorphisms, Β-globin gene frameworks and four variable number of tandem repeats (VNTRs). By combining the results of these analyses, we were able to rule out nonpaternity and to confirm the de novo nature of the mutation.
Elevated Levels of Markers of Endothelial Cell Damage and Markers of Activated Coagulation in Patients with Systemic Necrotizing Vasculitis
Authors: Hergesell Olaf , Andrassy Konard , Nawroth Peter 
Published: July 2018

SummaryActivation of coagulation and endothelial cell damage was studied in 47 patients with small vessel vasculitis [Wegener’s granulomatosis (WG) and microscopic polyangiitis (MP)] by measurement of throm-bin-antithrombin III complexes (TAT), fibrin-D-dimers (D-dimers), von Willebrand-factor (vWF) concentration and plasma thrombomodulin (TM) levels. There was a close correlation between disease activity (DA) in patients with WG or MP and markers of endothelial cell damage (correlation TM/DA r = 0.46 for WG and r = 0.43 for MP) and activated coagulation (correlation TAT/DA r = 0.58 for WG and r = 0.55 for MP).Elevation of the markers of activated haemostasis and endothelial cell damage was reversed when remission was obtained by specific treatment. The markers studied were particularly helpful in cases where measurement of antineutrophil cytoplasmatic antibodies (ANCA) did fail to assess disease activity.
Localization of Fibrinolytic Activators and Inhibitors in Normal and Atherosclerotic Vessels
Authors: Fålkenberg Marten , Tjärnstrom Johan , Örtenwall Per , Olausson Michael , Risberg Bo 
Published: July 2018

SummaryLocal fibrinolytic changes in atherosclerotic arteries have been suggested to influence plaque growth and promote mural thrombosis on ruptured or ulcerated plaques. Increased levels of plasminogen activator inhibitor (PAI-1) have been found in atherosclerotic arteries. In this study tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and PAI-1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemis-try. The expression of fibrinolytic regulators was related to the distribution of endothelial cells (EC) and macrophages. Results: t-PA was expressed in vasa vasorum. PAI-1 was positive in endothelial cells, in the media and in the adventitia. Increased expression of t-PA, u-PA and PAI-1 was found in atherosclerotic vessels. t-PA, u-PA, PAI-1 and macrophages were co-localized in plaques. These results support the concept that macrophages can be important in the local regulation of fibrinolysis in atherosclerotic vessels.
The Potential Thrombogenic Action of a Nonionic Radiographic Contrast Medium Used during Coronary Angiography Is Offset by Heparin during Coronary Angioplasty
Authors: Mukherjee Manjari , Scully Michael F , Thomas Martin , Jewitt David , Kakkar Vijay V 
Published: July 2018

SummaryIohexol sodium, a nonionic radiographic contrast medium, used in invasive imaging techniques has been shown to be potentially thrombogenic. In the present study, the effect of iohexol sodium on haemostatic factors was evaluated in 20 patients, 16 male and 4 female, 10 undergoing coronary angiography and another 10 undergoing coronary angioplasty. All the patients had angiographically-assessed coronary artery disease. The patients undergoing coronary angioplasty received a significantly larger quantity of the dye as compared with the patients undergoing coronary angiography. The former group of patients also received a bolus of 20,000 units of standard heparin in addition. The levels of thrombin-antithrombin-III complex (TAT), prothrombin fragments 1 and 2 (F1F2), D-dimer and the functional activity of tissue factor pathway inhibitor (TFPI) were assayed. While the baseline and 30-min post-dye levels of TAT and F1F2 were comparable in patients undergoing coronary angioplasty, the 30 min levels were significantly elevated in patients undergoing coronary angiography. The post-dye levels of TFPI activity were significantly increased in the former group due to the heparin-induced release of TFPI. It is concluded that the thrombogenic potential of iohexol sodium was overcome by heparin used routinely during coronary angioplasty.
Free Protein S Deficiency May Be Found in Patients with Antiphospholipid Antibodies who Do not Have Systemic Lupus Erythematosus
Authors: Crowther M A , Johnston M , Weitz J , Ginsberg J S 
Published: July 2018

SummaryIn order to determine if there is a relationship between antiphospholipid antibodies and reduced free protein S levels, we evaluated 21 patients who had an antiphospholipid antibody but had neither a history of venous thromboembolism nor systemic lupus erythematosus (cases) and 55 matched controls, who did not have an antiphospholipid antibody, a history of thrombosis or systemic lupus erythematosus. Cases and controls had similar protein C and antithrombin levels. Six of 21 cases had reduced free protein S antigen levels, compared to 5 of 55 controls (x
2 = 5.823 p <0.025). In addition, the mean free protein S level was significantly lower in cases than in controls (0.30 ± 0.09 units vs 0.39 ± 0.13 units, p <0.01, two-tailed Student’s t-test). We conclude that antiphospholipid antibodies are associated with a significant decrease in free protein S levels, and that this acquired free protein S deficiency may contribute to the thrombotic diathesis seen in patients with antiphospholipid antibodies.
Interleukin-6 Stimulates Coagulation, not Fibrinolysis, in Humans
Authors: Stouthard Jacqueline M L , Levi Marcel , Hack C Erik , Veenhof Cees H N , Romijn Hans A , Sauerwein Hans P , Poll Tom van der 
Published: July 2018

SummaryThe role of IL-6 as a mediator of haemostatic changes during severe inflammation is controversial. To assess the effect of IL-6 on haemostasis we conducted a controlled cross-over study in eight patients with metastatic renal cell cancer. In all subjects coagulation and fibrinolysis were monitored during and after a 4-h infusion of either 150 μg recombinant human (rh) IL-6, or during infusion of saline (control study). Mean maximum IL-6 concentrations were 1418.0 ± 755.8 pg/ml. Compared to the control study, rhIL-6 induced activation of coagulation as reflected by a 190 ± 55% increase in the plasma levels of thrombin-antithrombin III complexes (p <0.001) and by a 24 ± 11% increase in the plasma levels of in the prothrombin activation fragment F1 + 2 (p <0.001). In contrast, fibrinolysis was not affected. We conclude that in severe inflammation IL-6 may contribute to the activation of coagulation, whereas other factors mediate changes in fibrinolysis.
Decreased Expression of PAI-2 mRNA and Protein in Pregnancies Complicated with Intrauterine Fetal Growth Retardation
Authors: Grancha Salvador , Estellés Amparo , Gilabert Juan , Chirivella Melitina , España Francisco , Aznar Justo 
Published: July 2018

SummaryAn increase in plasma plasminogen activator inhibitors (PAIs), fundamentally PAI type 2 (PAI-2), has been described in normal pregnancy probably because the placenta is the main source of the high plasma levels of this protein. Although we have previously described plasmatic alterations of these inhibitors in pregnancies complicated with intrauterine fetal growth retardation (IUGR), no reports have been published about placental PAI-2 mRNA expression. In the present study, the placental PAI-2 expression determined in pregnancies complicated with IUGR and in severe preeclamptic patients was compared with that of normal pregnancies in order to identify the placental cell types expressing PAI-2 and to determine whether the production of PAI-2 is altered in placentas from IUGR. In situ hybridization analyses show that the syncytiotrophoblasts are the cells with the greatest PAI-2 expression in placenta. We report that the significant decrease in plasma and placental PAI-2 levels in IUGR groups is fundamentally due to a diminished expression of PAI-2 mRNA in placenta.
Inhibitory Effect of a Novel Orally Active GP IIb/IIIa Inhibitor, SC-54684A on Intimal Thickening in the Guinea Pig Femoral Artery
Authors: Umemura Kazuo , Nishiyama Hiroshi , Kikuchi Shinji , Kondo Kazunao , Nakashima Mitsuyoshi 
Published: July 2018

SummaryThe inhibitory effect of a novel orally active platelet membrane glycoprotein receptor complex IIb/IIIa (GP IIb/IIIa) inhibitor, SC-54684A is studied on intimal thickening in the guinea pig femoral artery. A segment of the femoral artery was occluded by a platelet-rich thrombus induced by photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after successful thrombolysis by tissue-type plasminogen activator, intimal thickening occurred at the irradiated site. SC-54684A (30 mg/kg), administered 2 h before photochemical reaction, significantly (P <0.05) prolonged the time to occlusion of the femoral artery; in this respect aspirin (100 mg/kg) was ineffective. A combination of SC-54684A and recombinant tissue-type plasminogen activator (rt-PA) increased the frequency of reopening and significantly (P <0.05) prolonged the duration of reflow compared with rt-PA alone. Further, SC-54684A administered orally twice a day for 3 weeks significantly (P <0.05) inhibited intimal thickening but aspirin, administered orally once a day for 3 weeks, was ineffective. Scanning electron microscopy revealed extensive platelet adhesion and aggregation on the denuded vessel walls in the untreated group 24 h after successful thrombolysis. In separate experiments, SC-54684A markedly inhibited platelet aggregation ex-vivo. Inhibition of platelet adhesion and aggregation at the site of endothelial injury by SC-54684A (via GPIIb/IIIa inhibition) may account for its inhibitory effect on intimal thickening
Procoagulant Properties of Intravenous Staphylokinase Versus Tissue-Type Plasminogen Activator
Authors: Okada K , Lijnen H R , Moreau H , Vanderschuere S , Collen D 
Published: July 2018

SummaryThe fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assigned to a double bolus (15 mg each, 30 min apart) administration of Sak42D or to accelerated weight-adjusted rt-PA (maximum of 100 mg over 90 min). Baseline levels of fibrinopeptide A (FPA), prothrombin fragment 1+2 and thrombin-antithrombin III complex (TAT) were comparable in the Sak42D and rt-PA groups (p ≥ 0.6). In patients treated with Sak42D, plasma levels of FPA, prothrombin fragment 1+2 and TAT did not markedly increase during treatment (p = 0.06, p = 0.4 and p = 0.03, respectively). In contrast, during administration of rt-PA the levels of FPA, prothrombin fragment 1+2 and TAT increased significantly over baseline (p = 0.003, p < 0.0001 and p = 0.001, respectively). As a result, the levels of all three procoagulant parameters were significantly lower during treatment with Sak42D as compared to rt-PA. Thus, FPA levels in the Sak42D group (median values) were 40 ng/ml at 25 min and 11 ng/ml at 90 min, as compared to 88 ng/ml and 50 ng/ml in the rt-PA group (p = 0.0007 and p = 0.009, respectively). Prothrombin fragment 1+2 levels in the Sak42D group were 1.3 nM at 25 min and 1.2 nM at 20 min, as compared to 11 nM and 5.3 nM in the rt-PA group (both p < 0.0001). TAT levels were 4.7 ng/ml at 25 min and 6.2 ng/ml at 90 min in the Sak42D group, with corresponding values of 16 ng/ml and 9.6 ng/ml in the rt-PA group (p = 0.02 and p = 0.03, respectively).In the patients treated with Sak42D, no significant systemic fibrinolytic activation was observed, as revealed by unaltered levels of clotta-ble fibrinogen, plasminogen and a2-antiplasmin up to 90 min after the start of therapy. In contrast, the corresponding residual levels at 90 min in patients treated with rt-PA decreased to (mean ± SEM; n = 12) 62 ± 6%, 45 ± 5% and 52 ± 10%, respectively (all p < 0.01 versus the Sak42D group)These data confirm the high degree of fibrin-specificity of Sak42D and demonstrate that this is associated with significantly less generation of procoagulant activity in plasma after intravenous administration in patients with acute myocardial infarction
Gene Mutations in 21 Unrelated Cases of Phenotypic Heterozygous Protein C Deficiency and Thrombosis
Authors: Ireland H , Thompson E , Lane D A ,   Protein C Study Group
Published: July 2018

SummaryMutations have been identified in the protein C gene in 21 patients with venous thromboembolism and phenotypic heterozygous protein C deficiency. In 20 probands, single mutations were the only abnormalities identified by sequencing all coding regions, intron exon boundaries and the promoter region back to -1540. In one proband 2 mutations were identified and in another family 2 mutations were identified (but not both in the proband). Of the 23 mutations, 18 resulted in predicted amino acid substitutions, 3 were mutations resulting in stop codons, one was a mutation within a consensus splice sequence and another a 9 base pair insertion within exon 5 (this region within exon 5 is proposed as a deletion/insertion hot spot). A novel polymorphism was also, uniquely, identified in the propeptide region of the molecule (Pro-21 Pro; CCT to CCC) in a kindred from Hong Kong. Cosegregation of the protein C gene mutation with protein C deficiency could be determined in 13 families. In a further family, phenotypic protein C deficiency and the genetic mutation cosegregated in only 4/5 members.The first thrombotic incident occurred in the probands between the ages of 11 and 59 years and 12 individuals suffered recurrent thrombosis. Thrombosis occurred in at least one other family member in 9/21 families, but in 2 of these it was inconsistently associated with protein C deficiency. An independent genetic risk factor, factor V Arg506Gln (FV Leiden) was identified in 2 probands (and 3 family members) and in 4 protein C deficient members of a third family but not in the proband. The results suggest that in the majority of probands with thrombosis and phenotypic protein C deficiency, a single protein C gene mutation is associated with thrombosis. However, it is also possible that additional unknown genetic risk factors contribute to the thrombotic risk. An added, acquired, risk factor leads to thrombosis at an early age (< 25 years).