bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the contribution of the Megha‐Tropiques mission to the estimation of daily accumulated rainfall in the Tropics
Authors: Roca Rémy , Taburet Nicolas , Lorant Estelle , Chambon Philippe , Alcoba Matias , Brogniez Hélène , Cloché Sophie , Dufour Christophe , Gosset Marielle , Guilloteau Clément
Published: June 2018

Satellite estimation of accumulated precipitation is an important facet of the study of the tropical water cycle. An advanced data merging approach using infrared geostationary imagery and microwave constellation based instantaneous rain rate estimates has been implemented in the framework of the Megha‐Tropiques and Global Precipitation Measurements missions. The Tropical Amount of Rainfall with Estimation of ERors (TAPEER) algorithm has been tailored to account for the loss of the MADRAS conical scanning radiometer by using the SAPHIR sounder rainfall detection capability, thanks to a novel two‐constellation implementation of the algorithm. A new bias correction module based on the TRMM PR observations is also presented. The performances of this new version of the product are reviewed with emphasis on West Africa. In particular, using data‐denial experiments, the contribution of SAPHIR data to the rainfall daily accumulation is quantified for various configurations of the microwave constellation and various algorithmic parameter selections. The results show that the daily accumulation statistics are well improved when SAPHIR is taken into the constellation. The improvements can be quantified using bulk statistics but are more evident following a frequency analysis. The pattern of the impact is a complex convolution of rainfall occurrence and of the Megha‐Tropiques mission original sampling. Over the 20°N–20°S belt, in zonal mean, the inclusion of SAPHIR data alters the daily accumulation substantially (more than 50% of the daily accumulation) more than 10% of the time and more than 20% when conditioned upon rainfall. Under both metrics, the improvement is majored in the 12°–17° latitude band where the Megha‐Tropiques mission sampling is at its maximum.
Characteristics of colliding density currents: A numerical and theoretical study
Authors: Cafaro Carlo , Rooney Gabriel G.
Published: June 2018

This paper presents a new set of numerical simulations of two colliding density currents in a idealized framework, integrating the Boussinesq vorticity equation in a rectangular bounded domain. These simulations are used to examine the dynamical features of the collision, in the light of recent laboratory experiments. The collision dynamics present various interesting features. Here we have focused on the interface slope at the front of the two unequal density currents and on the maximum height reached by the fluid after the collision. For the secondary triggering of atmospheric convection by colliding cold pools from previous convective events, these may affect the positioning and the momentum of the collision uplift, respectively.

The interface slope has been shown to be dependent on the currents' buoyancy ratio (i.e. the ratio between the density differences of the two fluids with the ambient fluid), whereas the maximum height has no strong dependence, for a given initial current depth. A theoretical model, based on an analogy with a vortex pair, has been proposed for the interface‐slope dependence, taking as input the buoyancy ratio or the propagating speeds. This model agrees reasonably well with the observed numerical values.
Information constraints in variational data assimilation
Authors: Kahnert Michael
Published: June 2018

Data assimilation of indirect observations from remote‐sensing instruments often leads to highly under‐determined inverse problems. Here a formulation of the variational method is discussed in which (a) the information content of the observations is systematically analysed by methods borrowed from retrieval theory; (b) the model space is transformed into a phase space in which one can partition the model variables into those that are related to the degrees of freedom for signal and noise, respectively; and (c) the minimization routine in the variational analysis is constrained to act on the signal‐related phase‐space variables only. This is done by truncating the dimension of the phase space. A first test of the method indicates that the constrained analysis speeds up computation time by about an order of magnitude compared with the formulation without information constraints.
An atmospheric dynamics perspective on the amplification and propagation of forecast error in numerical weather prediction models: A case study
Authors: Grams Christian M. , Magnusson Linus , Madonna Erica
Published: June 2018

Despite huge progress made, state‐of‐the‐art numerical weather prediction systems occasionally experience severe forecast busts for the large‐scale extratropical circulation. This study investigates one of the most severe forecast busts for Europe in the European Centre for Medium‐Range Weather Forecasts integrated forecasting system (IFS) in recent years. The forecast bust occurred in March 2016 and was associated with a misforecast of the onset of a blocking regime. We investigate the evolution of the forecast error in the IFS ensemble by employing a potential vorticity perspective combined with Lagrangian diagnostics. We show that the error grows rapidly from an initially small perturbation in the detailed structure of an upper‐level trough near Newfoundland. This trough triggers strong diabatic warm conveyor belt activity in the North Atlantic region. The misrepresentation of this warm conveyor belt activity in the ensemble forecast amplifies the initial condition error and communicates it downstream into Europe. Specifically, the ensemble underestimates poleward warm conveyor belt ascent and associated warm conveyor belt outflow into high latitudes. Instead, all ensemble members forecast too strong warm conveyor belt outflow further to the south, which ultimately results in a wrong forecast of the upper‐level Rossby wave pattern over Europe. This case study shows that warm conveyor belts and the associated latent heat release in slantwise ascending air can trigger a nonlinear feedback mechanism that amplifies forecast error strongly and communicates it into regions far downstream. It corroborates the fact that multiscale interactions and moist‐and dry‐dynamical processes ranging from microphysical to synoptic scales need to be represented accurately in numerical weather prediction, in order to predict the extratropical large‐scale circulation correctly.
Evaluation of laser heterodyne radiometry for numerical weather prediction applications
Authors: Smith Fiona , Havemann Stephan , Hoffmann Alex , Bell William , Weidmann Damien , Newman Stuart
Published: June 2018

This article reports the results of a preliminary mission study to assess the potential of space‐borne laser heterodyne radiometry (LHR) for the remote sensing of temperature for assimilation in a numerical weather prediction (NWP) model. The LHR instruments are low cost and small in size, lending themselves to a wide variety of satellite platforms. The impact of different configurations of an idealized LHR instrument is assessed against the Infrared Atmospheric Sounding Interferometer (IASI), via single‐column linear information content analysis, using inputs consistent with the background errors of the Met Office 4D‐Var assimilation system. Multiplexed configurations give promising results, in particular for sounding of upper‐atmospheric temperatures.
Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring
Authors: Vousooghi Nasim , Sadat‐Shirazi Mitra‐Sadat , Safavi Payam , Zeraati Ramin , Akbarabadi Ardeshir , Makki Seyed Mohammad , Nazari Shahrzad , Zarrindast Mohammad Reza
Published: June 2018

Addiction to drugs, including opioids is the result of an interplay between environmental and genetic factors. It has been shown that the progeny of addict people is at higher risk for drug addiction. However, the mechanisms of such trans‐generational effects of drugs are not so clear. Here we have evaluated the effects of parental morphine consumption on anxiety, morphine preference, and mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was chronically administered to adult male and female Wistar rats followed by 14‐day abstinence before mating. Morphine preference and anxiety‐like behavior in the offspring were measured by two‐bottle‐choice paradigm and elevated‐plus maze, respectively. Real‐time PCR was used to measure the mRNA expression level of dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and hippocampus of F1 animals. The results indicated that F1 but not the F2 male progeny of morphine‐exposed parents had a greater preference for morphine, and more anxiety‐like behavior compared to the offspring of saline‐treated parents. In F1 male progeny of morphine‐treated parents, D1 and D5 dopamine receptors were significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2 receptors were decreased in the hippocampus. D4 dopamine receptor was augmented in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood exposure to chronic morphine in male and female rats before conception leads to higher morphine preference and increased anxiety in F1 but not F2 male progeny. Alterations of dopamine receptor expression in the reward system may be one mechanism responsible for observed changes in F1 offspring.
Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido‐inflammatory stress in rat model of autism
Authors: Khalaj Rashin , Hajizadeh Moghaddam Akbar , Zare Mahboobeh
Published: June 2018

Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido‐inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano‐hesperetin on social behavior deficits and oxido‐inflammatory indexes in prenatally valproic acid‐exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group‐1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group‐2 received sodium valproate (500 mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA‐exposed group, Group‐3 to 6 were VPA‐exposed which received hesperetin and nano‐hesperetin (10 and 20 mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid‐exposed rat exhibited poor sociability and high level of anxiety‐like behaviors (P <  0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido‐inflammatory markers. Hesperetin and nano‐hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p <  0.05) plasma's inflammation indexes. In conclusion, it can be state that nano‐hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation.
Prenatal undernutrition decreases the anorectic response to septic doses of lipopolysaccharides in adulthood in male rats
Authors: Iwasa Takeshi , Matsuzaki Toshiya , Yano Kiyohito , Mayila Yiliyasi , Irahara Minoru
Published: June 2018

Prenatal undernutrition affects some physiological functions after birth, and such changes are associated with the pathogenesis of various diseases. Recently, we have reported that prenatally undernourished male rats exhibited stronger febrile and anorectic responses to immune stress induced by moderate‐dose lipopolysaccharide (LPS) treatment in adulthood. In the present study, we evaluated the effects of prenatal undernutrition on stress responses to the administration of a septic dose (3 mg/kg) of LPS in later life, mainly focusing on changes in hypothalamic proinflammatory cytokine expression. We also evaluated the expression of hypothalamic and peripheral reproductive factors because it has been suggested that the stress responses of reproductive functions are affected by prenatal and neonatal stress and nutritional conditions. As a result, we found that prenatal undernutrition attenuated the anorectic response to septic‐dose LPS treatment in adulthood in male rats. In addition, it attenuated the LPS‐induced suppression of serum testosterone levels and the changes in hypothalamic proinflammatory cytokine (interleukin (IL)‐1β, tumor necrosis factor‐α, and IL‐6) expression induced by septic‐dose LPS treatment in adulthood. These results suggest that prenatal undernutrition attenuates stress and reproductive responses under severe immune stress conditions. The downregulation of hypothalamic stress‐related factor expression might be involved in such attenuated stress responses, which could be one of the protective mechanisms used to prevent excessive immune responses and aid survival.
Safety Considerations in Prescription of NSAIDs for Musculoskeletal Pain: A Narrative Review
Authors: Hatt Katie M. , Vijapura Anita , Maitin Ian B. , Cruz Ernesto
Published: June 2018

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are frequently prescribed for the treatment of painful musculoskeletal conditions. When prescribing oral NSAIDs, clinicians must consider coexisting cardiovascular, cerebrovascular, gastrointestinal, and renal disease because oral NSAIDs are associated with a broad spectrum of adverse effects on these systems. The different safety profiles of NSAIDs can be attributed to differences in the extent to which the drug inhibits cyclo‐oxygenase‐1 vs ‐2 and their potential for drug‐drug interactions. This narrative review intends to guide the clinician in prescribing oral NSAIDs while taking into consideration these comorbid conditions and drug interactions.

Level of Evidence

III
Pregnancy Results in Lasting Changes in Knee Joint Laxity
Authors: Chu Stacey R. , Boyer Elizabeth H. , Beynnon Bruce , Segal Neil A.
Published: June 2018

Background

Altered joint laxity can contribute to joint dysfunction. Knee joint laxity has been shown to increase during pregnancy, but its long‐term persistence is unknown.

Objective

To determine whether pregnancy leads to lasting increases in knee joint compliance and laxity that persist longer than 4 months postpartum.

Design

Prospective cohort study.

Setting

A motion analysis laboratory at an academic medical center.

Participants

Fifty healthy women in their first trimester of pregnancy (mean ± SD 29.2 ± 4.3 years old and baseline body mass index 26.0 ± 5.4 kg/m2) were recruited.

Intervention

End‐range knee laxity and midrange joint compliance were measured during the first trimester and 19 ± 4 weeks postpartum. Anterior‐posterior and varus‐valgus laxity were measured using 3‐dimensional motion tracking while applying forces and moments in each respective plane using the Vermont Knee Laxity Device. Nonlinear models were constructed to assess relations between applied forces and joint translation, comparing early pregnancy with postpartum.

Outcomes

Multiplanar knee laxity and compliance.

Results

Peak varus‐valgus (20‐22%; P = .001) and posterior translation (51%; P < .001) of the tibia relative to the femur decreased from baseline, with a concomitant decrease in laxity (P < .001) and compliance (P = .039) in the coronal plane and in the posterior direction in primiparous (P = .009) and multiparous (P = .014) women. For primiparous women, laxity (P < .001) and compliance (P = .009) increased in the anterior direction.

Conclusions

Pregnancy resulted in a lasting decrease in multiplanar knee laxity and compliance in the varus and posterior directions with an increase in anterior compliance. The effects of these changes in laxity and compliance of the passive stabilizers on knee loading patterns, articular contact stresses, and risk for osteoarthritis and other musculoskeletal disorders will require additional research.

Level of Evidence

II
Can a Brief Training Session Prepare Physician Sonographers of Differing Experience to Measure the Ischiofemoral Space? A Reliability Study
Authors: Boettcher Brennan J. , Hollman John H. , Payne Jeffrey M. , Johnson Adam C. , Finnoff Jonathan T.
Published: June 2018

Objective

The primary aim of this study was to determine the inter‐ and intrarater reliability of ultrasound (US) measurements of the ischiofemoral space (IFS) following a brief training session. A secondary aim was to determine if reliability correlated with sonographer experience.

Design

Prospective cohort study.

Setting

Physical medicine and rehabilitation department within a tertiary care institution.

Participants

Seven male and 3 female individuals were recruited to serve as models. Nine physician sonographers (3 postgraduate year [PGY]‐2 residents, 3 PGY‐4 residents, 3 physicians) were recruited to serve as sonographers.

Methods or Interventions

Sonographers received a 15‐minute educational session on identifying the IFS with US, followed by 20 minutes of practice. Models were then placed in a prone position and secured to prevent hip movement. All operators measured bilateral IFSs in each model twice with a washout period between measurements. Operators were blinded to all measurements.

Main Outcome Measures

Primary outcomes were inter‐ and intrarater reliability interclass coefficients (ICCs) of IFS measurements among the groups with different levels of US experience. Secondary outcomes included comparisons of inter‐ and intrarater reliability ICCs of IFS measurements between groups, and the difference of mean IFS measurements between groups.

Results

Intrarater reliability ICCs were 0.829, 0.680, and 0.596 for physician, PGY‐4, and PGY‐2 groups, respectively. Interrater reliability ICCs were 0.722, 0.427, and 0.558 for physician, PGY‐4, and PGY‐2 groups, respectively. No statistically significant differences in reliability were identified between groups. Mean IFS measurements were 31.2, 33.4, and 34.0 mm for physician, PGY‐4, and PGY‐2 groups, respectively. Physician measurements were significantly smaller than the PGY‐4 and PGY‐2 measurements (P < .049 and P < .01).

Conclusions

Following a brief training session, experienced sonographers demonstrated excellent IFS measurement intrarater reliability, whereas PGY‐4 and PGY‐2 sonographers demonstrated fair intrarater reliability. All sonographers demonstrated fair interrater reliability.

Level of Evidence

II
Stemming the tide of illiberalism? Legal mobilization and adversarial legalism in Central and Eastern Europe
Authors: Şerban Mihaela
Published: June 2018

This paper explores the rise of rights-based regulation through litigation as a distinctive feature of legal culture in Central and Eastern Europe post-1989. This type of adversarial legalism was born at the intersection of post-communist, European integration, and neoliberal discourses, and is characterized by legal mobilization at national and supranational levels, selective adaptation of adversarial mechanisms, and the growth of rights consciousness. The paper distinguishes Eastern European developments from both American and Western European types of adversarial legalism, assesses the first quarter century of post-communism and represents a first step towards constructing a genealogy of the region’s legal culture post-1989.
Variations in Denitrification and Ventilation Within the Arabian Sea Oxygen Minimum Zone During the Holocene
Authors: Kessarkar Pratima M. , Naqvi S. W. A. , Thamban M. , Fernandes Lina L. , Siebert Christopher , Rao V. Purnachandra , Kawahata H. , Ittekkot V. , Frank Martin
Published: June 2018

The continental slope of India is exposed to an intense perennial oxygen minimum zone (OMZ) supporting pelagic denitrification. Sediments that are presently in contact with the lower boundary of the denitrification zone indicate marked changes in the intermediate and bottom waters ventilation of OMZ during the past 9,500 years. The δ15N of sediment suggests that the OMZ waters were less ventilated during the early Holocene (between 9.5 and 8.5 ka BP) resulting in intensified denitrifying conditions with an average δ15N value of 7.8‰, while at the same time stable Mo isotope composition (average δ98Mo of −0.02‰) indicates that the bottom waters that were in contact with the sediments were better oxygenated. By the mid‐Holocene OMZ became more oxygenated suppressing denitrification (average δ15N of 6.2‰), while bottom waters gradually became less oxygenated (average δ98Mo of 1.7‰). The mid‐Holocene reduction in denitrification coincided with a global decrease in atmospheric N2O as inferred from ice core records, which is consistent with a decreased contribution from the Arabian Sea. Since ~5.5 ka BP OMZ waters have again been undergoing progressive deoxygenation accompanied by increasing denitrification.
The Tiny Organisms That Transport Silica Across Earth’s Oceans
Authors: Underwood Emily
Published: June 2018

Phaeodarians play a major role in marine nutrient cycle.
Plasma Anisotropies and Currents in the Near‐Earth Plasma Sheet and Inner Magnetosphere
Authors: Artemyev A. V. , Zhang X.‐J. , Angelopoulos V. , Runov A. , Spence H. E. , Larsen B. A.
Published: June 2018

The region occupying radial distances of ∼3–9 Earth radii (RE) in the nightside includes the near‐Earth plasma sheet with stretched magnetic field lines and the inner magnetosphere with strong dipolar magnetic field. In this region, the plasma flow energy, which was injected into the inner magnetosphere from the magnetotail, is converted to particle heating and electromagnetic wave generation. These important processes are controlled by plasma anisotropies, which are the focus of this study. Using measurements of Time History of Events and Macroscale Interactions during Substorms and Van Allen Probes in this transition region we obtain radial profiles of ion and electron temperatures and anisotropies for various geomagnetic activity levels. Ion and electron anisotropies vary with the geomagnetic activity in opposite directions. Parallel anisotropic ions are observed together with transversely anisotropic electrons, whereas the change of ion anisotropy from parallel to transverse (with increasing Kp) is accompanied by the electron anisotropy changing from transverse to parallel. Based on plasma anisotropy observations, we estimate that the anisotropy‐related currents (curvature currents) are about 10–20% of the diamagnetic currents.
Statistical Investigation of the Efficiency of EMIC Waves in Precipitating Relativistic Electrons
Authors: Qin Murong , Hudson Mary , Millan Robyn , Woodger Leslie , Shekhar Sapna
Published: June 2018

Electromagnetic ion cyclotron (EMIC) waves have been proposed to cause relativistic electron precipitation (REP). In our study, we carry out 4 years of analysis from 2013 to 2016, with REP spikes obtained from POES satellites and EMIC waves observation from Van Allen Probes. Among the 473 coincidence events when POES satellites go through the region conjugate to EMIC wave activity, only 127 are associated with REP. Additionally, the coincidence occurrence rate is about 10% higher than the random coincidence occurrence rate, indicating that EMIC waves and relativistic electrons can be statistically related, but the link is weaker than expected. H+ band EMIC waves have been regarded as less important than He+ band EMIC waves for the precipitation of relativistic electrons. We demonstrate that the proportion of H+ band EMIC wave events that are associated with REP (22% to 32%) is slightly higher than for He+ band EMIC wave activity (18% to 27%). An even greater proportion (25% to 40%) of EMIC waves are accompanied by REP events when H+ band and He+ band EMIC waves occur simultaneously.
Nitramino-functionalized tetracyclic oxadiazoles as energetic materials with high performance and high stability: crystal structures and energetic properties
Authors: Sun Qi , Lin Qiuhan , Lu Ming
Published: June 2018

The combination of 1,2,4-oxadiazole and nitramino-1,2,5-oxadiazole is a promising strategy for designing energetic materials with high performance and high stability.
Origin of fast oxide ion diffusion along grain boundaries in Sr-doped LaMnO3
Authors: Polfus Jonathan M. , Yildiz Bilge , Tuller Harry L.
Published: June 2018

Enhanced oxide ion diffusion by 3 to 5 orders of magnitude along grain boundary core in Sr-doped LaMnO3.
Crystal‐less oscillator calibration using serial data as frequency reference
Authors: Yang Wendi , Jiang Hanjun , Wang Zhihua
Published: June 2018

A frequency calibration method for a crystal‐less current‐controlled ring oscillator is presented. It uses a serial data signal from another chip as the frequency reference. The proposed calibration circuit is composed of the coarse calibration and the fine calibration circuit. The coarse calibration circuit controls a binary weighted biasing current source array, while the fine calibration circuit generates a pulse‐width‐modulation (PWM) signal to control a switched biasing current source. The duty cycle ratio of the PWM signal is obtained by measuring the frequency ratio error between the oscillator output and the reference signal. An auto‐correlation‐based method is proposed to calculate the frequency ratio error. The 8 MHz ring oscillator in together with the calibration circuit has been fabricated in a 0.13 μm CMOS process. Measured results on 24 chips show that the relative frequency error is reduced to 0.0239% (mean offset + 3σ) after calibration. The reported oscillator shows advantages in accuracy, power consumption and chip area.
ZSI for PV systems with LVRT capability
Authors: Sajadian Sally , Ahmadi Reza
Published: June 2018

This study proposes a power electronics interface (PEI) for photovoltaic (PV) applications with a wide range of ancillary services. As the penetration of distributed generation systems is booming, the PEI for renewable energy sources should be capable of providing ancillary services such as reactive power compensation and low‐voltage ride through (LVRT). This study proposes a robust model predictive‐based control strategy for grid‐tied Z‐source inverters (ZSIs) for PV applications with LVRT capability. The proposed system has two operation modes: normal grid condition and grid fault condition modes. In normal grid condition mode, the maximum available power from the PV panels is injected into the grid. In this mode, the system can provide reactive power compensation as a power conditioning unit for ancillary services from DG systems to main ac grid. In case of grid faults, the proposed system changes the behaviour of reactive power injection into the grid for LVRT operation according to the grid requirements. Thus, the proposed controller for ZSI is taking into account both the power quality issues and reactive power injection under abnormal grid conditions. The proposed system operation is verified experimentally, the results demonstrate fast dynamic response, small tracking error in steady‐state, and simple control scheme.
Gaia Data Release 2
Authors: Arenou F. , Luri X. , Babusiaux C. , Fabricius C. , Helmi A. , Muraveva T. , Robin A. C. , Spoto F. , Vallenari A. , Antoja T. , Cantat-Gaudin T. , Jordi C. , Leclerc N. , Reylé C. , Romero-Gómez M. , Shih I.-C. , Soria S. , Barache C. , Bossini D. , Bragaglia A. , Breddels M. A. , Fabrizio M. , Lambert S. , Marrese P. M. , Massari D. , Moitinho A. , Robichon N. , Ruiz-Dern L. , Sordo R. , Veljanoski J. , Eyer L. , Jasniewicz G. , Pancino E. , Soubiran C. , Spagna A. , Tanga P. , Turon C. , Zurbach C.
Published: June 2018

Context. The second Gaia data release (DR2) contains very precise astrometric and photometric properties for more than one billion sources, astrophysical parameters for dozens of millions, radial velocities for millions, variability information for half a million stars from selected variability classes, and orbits for thousands of solar system objects.

Aims. Before the catalogue was published, these data have undergone dedicated validation processes. The goal of this paper is to describe the validation results in terms of completeness, accuracy, and precision of the various Gaia DR2 data.

Methods. The validation processes include a systematic analysis of the catalogue content to detect anomalies, either individual errors or statistical properties, using statistical analysis and comparisons to external data or to models.

Results. Although the astrometric, photometric, and spectroscopic data are of unprecedented quality and quantity, it is shown that the data cannot be used without dedicated attention to the limitations described here, in the catalogue documentation and in accompanying papers. We place special emphasis on the caveats for the statistical use of the data in scientific exploitation. In particular, we discuss the quality filters and the consideration of the properties, systematics, and uncertainties from astrometry to astrophysical parameters, together with the various selection functions.
Maligne Knochentumoren im Kindesalter
Authors: Uhl Markus , Hettmer Simone , Herget Georg
Published: June 2018

Das Osteosarkom und das Ewing-Sarkom als häufigste primäre maligne Knochentumoren im Kindesalter sind Tumoren mit vielen Gesichtern. Ihre Malignität erfordert eine rechtzeitige Diagnose und die sichere Abgrenzung von anderen aggressiven Knochentumoren, z. B. von der Langerhans-Zell-Histiozytose.
Einsparpotenziale für die medikamentöse Therapie des Prostatakrebs sind in der GKV regional unterschiedlich
Authors: de Millas Christoph , Zimmermann Anne , Höer Ariane
Published: June 2018

Zielsetzung Gonadotropin-Releasing-Hormon-Analoga (GnRH-Analoga) sind der Therapiestandard bei der Behandlung von fortgeschrittenem Prostatakrebs. Vier
GnRH-Analoga (Buserelin, Goserelin, Leuprorelin und Triptorelin) waren 2015 und 2016 verfügbar. Nur Leuprorelin war generisch verfügbar. Es wurde modelliert, ob
für die gesetzlichen Krankenkassen Einsparpotenziale im Bereich der GnRH-Analoga bestehen, wenn regionale Unterschiede im Verschreibungsverhalten aufgehoben
werden.

Methodik Datengrundlage waren monatliche ambulante Verordnungsdaten von IQVIA auf Ebene der Kassenärztlichen Vereinigungen (KVen) und gesetzlichen
Krankenkassen (GKV). Auf Basis von zwei Benchmarks wurden regionale Einsparpotenziale berechnet. Der erste Benchmark ist die größte beobachtete
Marktdurchdringung nach Verbrauch – gemessen in definierten Tagesdosen (DDD) – in einem Quartal 2015/2016 in einer KV-Region in Bezug auf den wirtschaftlichsten
Wirkstoff. Der zweite Benchmark ist innerhalb des wirtschaftlichsten Wirkstoffs die größte beobachtete Marktdurchdringung des preisgünstigsten Produktes.

Ergebnisse Die Umsätze des GnRH-Marktes in der GKV waren 2015 und 2016 mit 207,7 Mio. bzw. 212,3 Mio. relativ stabil. Leuprorelin war mit einem
Marktanteil von 69,9 % (Q4 2016) das umsatzstärkste GnRH-Analogon. Innerhalb des Leuprorelin-Marktes ist der Erstanbieter mit 59,6 % Marktführer, während das
einzige Generikum im Markt einen Anteil von 18,1 % erreichte (Q4 2016). Leuprorelin-Generika (4,51 Euro/DDD) stellen die wirtschaftlichste Alternative im
Vergleich zu den übrigen Leuprorelin-Produkten (5,55 Euro/DDD) bzw. GnRH-Analoga (6,02 Euro/DDD) dar. Die Marktanteile nach Verbrauch (DDD) schwankten in den
KVen für Leuprorelin im Q4 2016 zwischen 63,0 % und 79,7 %. Innerhalb des Leuprorelin-Marktes lagen die regionalen Generikaanteile zwischen 7,8 % und 39,5 %.
Dabei wurde in KVen mit „Leitsubstanzquoten“ im Beobachtungszeitraum tendenziell höhere Einsparpotentiale erzielt. Regelungen zu Gunsten von Leuprorelin hatten
im Betrachtungszeitraum vier von 17 KVen. In fünf KVen wurde eine entsprechende Regelung 2017 neu eingeführt. Die GKV hätte 2015 und 2016 insgesamt 20,6 Mio.
Euro einsparen können, wenn in allen KV-Regionen die Benchmarks erreicht worden wären.

Schlussfolgerung Die Ergebnisse zeigen einen niedrigen Marktanteil für das Leuprorelin-Generikum und starke regionale Unterschiede in der Marktverteilung.
Klassische Instrumente der GKV zur Förderung von Generika greifen in diesem Fall nicht. Leitsubstanzregelungen können eine wirtschaftliche Verordnungsweise
fördern, indem sie die Marktdurchdringung von Generika erhöhen. Sie werden daher verstärkt vereinbart. Es sind dadurch substantielle Einsparungen bei
gleichbleibender Versorgungsqualität möglich.
Plasminogen Activator Inhibitor-1 Levels in Patients with Chronic Angina Pectoris with or without Angiographic Evidence of Coronary Sclerosis
Authors: Huber K , Resch I , Stefenelli Th , Lang I , Probst P , Kaindl F , Binder B R
Published: June 2018

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent ui pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p <0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction t-PA antigen was also elevated m CAD patients as compared to the non-CAD group (p <0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.
Effects of Moderate Alcohol Consumption on Platelet Function, Tissue-Type Plasminogen Activator and Plasminogen Activator Inhibitor
Authors: Veenastra J , Kluft C , Ockhuizen Th , Pol H v d , Wedel M , Schaafsma G
Published: June 2018

Short-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20–30 and 45–55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.
The Increased Rate of Activation of Factor XII in Late Pregnancy Can Contribute to the Increased Reactivity of Factor VII
Authors: Mitropoulos K A , Martin J C , Burgess A I , Esnouf M P , Stirling Y , Howarth D J , Reeves B E A
Published: June 2018

The amidolytic activity of enzymes derived from factor XII (XIIa) was 3-fold higher in plasmas collected during pregnancy than from control subjects. Factor VII coagulant activity (VIIc) and XIIa increased in both kinds of plasmas on incubation on ice for 24 h (cold activation). These increases could be attributed to the decreased potency of C1 inhibitor (C1INH). However, variations in the concentration of C1INH and of factor XII could not explain the differences in VIIc and in XIIa between late pregnancy and control plasmas following cold activation under the same conditions. It is concluded that in vitro the increased amount of contact surface in the late pregnancy plasma promotes a higher rate of generation of XIIa and consequently a higher rate of activation of factor VII. The increased amount of contact surface could also be responsible for the increased concentration of XIIa in non-treated plasma from late pregnancy and could contribute in vivo to the higher reactivity of factor VII in this condition.
Relation of Intraperitoneal and Intravascular Coagulation and Fibrinolysis Related Antigens in Peritoneal Dialysis
Authors: Gries E , Kopp J , Thomae U , Kuhlmann H
Published: June 2018

Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition.

We found an intraperitoneal fibrinogen cleavage and thrombin- antithrombin Ill-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 ± 7.0 ng/ml) and thrombin-antithrombin Ill-complex (TAT: 4.7 ± 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well.

The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.
Contribution of Platelets to Increased Plasminogen Activator Inhibitor Type 1 in Severe Preeclampsia
Authors: Gilabert Juan , Estellés Amparo , Aznar Justo , España Francisco , Andrés Cristina , Santos Teresa , Vallés Juana
Published: June 2018

Plasminogen activator inhibitor activity and antigen were evaluated in plasma, serum and platelet lysate in patients with severe preeclampsia (n = 12), and in normal pregnant women (n = 21). Other parameters, including β-thromboglobulin and platelet count, were also evaluated. A significant increase (p <0.05) in β-thromboglobulin was observed in platelet poor plasma of preeclamptic women when compared with that of normal pregnant women, and the platelet count was lower in the preeclamptic group than in the normal pregnant group. A significant increase in plasminogen activator inhibitor activity and antigen was observed in platelet poor plasma of the preeclamptic group as compared with normal pregnant women, whereas platelet lysate from preeclamptic women showed a significant decrease in both plasminogen activator inhibitor activity and antigen as compared with that of normal pregnant women. No correlation between β-thromboglobulin and plasminogen activator inhibitor type 1 antigen in platelet poor plasma was observed, but a significant inverse correlation (r = −0.78, p <0.05) between β-thromboglobulin in platelet poor plasma and plasminogen activator inhibitor-1 antigen in platelet lysate was obtained in preeclamptic patients. However, in platelet poor plasmas obtained from normal platelet rich plasmas activated with thrombin (0.1 IU/ml, 37° C, 1 min), an increase of about 300 ng/ ml in β-thromboglobulin was observed while the increase in plasminogen activator inhibitor was only 4 ng/ml. It is concluded that the contribution of platelet plasminogen activator inhibitor-1 to the increase in plasma plasminogen activator inhibitor-1 levels in preeclamptic patients is negligible but the possibility that intravascular platelet activation indirectly contributes “in vivo” to the increase in plasma plasminogen activator inhibitor-1 levels in severe preeclampsia patients cannot be ruled out.
Awareness of High Blood Pressure Stimulates Platelet Release Reaction
Authors: Rostrup Morten , Mundal Håvard Holth , Kjeldsen Sverre Erik , Gjesdal Knut , Eide Ivar
Published: June 2018

The present study aimed at testing the hypothesis of a link between mental stress and blood platelet function. Twenty-nine 19-year-old men were recruited from the 98th percentile of mean blood pressure (116 mmHg) at a routine medical screening. They were not informed about their elevated blood pressures at the time of the screening. One year later they were randomized into two groups. Group 1 (n = 16) was exposed to mental stress by a letter informing them about their high blood pressure, while group 2 (n = 13) was sent a neutral letter. At an examination 2 weeks later, heart rate (p <0.05) and plasma adrenaline (p <0.05) responses to a cold pressor test were exaggerated in the informed group. The plasma beta-thromoglobulin (pTG) concentration was elevated in the informed group (p <0.05) as was mean blood pressure (p <0.05). (3TG correlated positively with hematocrit (r = 0.59, p <0.005) and mean blood pressure (r = 0.43, p <0.05), and negatively with plasma HDL (r = −0.61, p = 0.001). The study shows that awareness of hypertension induces a hyperadrenergic state which is associated with the platelet release reaction. Under these circumstances platelet release seems to be correlated to established coronary heart disease risk factors.
β-TG and Plasma Catecholamines Levels after Sympathetic Stimuli in Hypertensives and Patients with Peripheral Vascular Disease
Authors: Catalano Maria , Russo Umberto , Belletti Sebastiano , Colombo Fabrizio , Belloni Armando , Rosso Gianfranco del , Lombardi Federico , Libretti Arnaldo
Published: June 2018

The influence of the sympathetic nervous system on platelet functions in vivo is still controversial. The aims of our study were to compare the response to various sympathetic stimuli in normal subjects and in patients with essential hypertension (HT) or peripheral vascular disease (PVD) and to evaluate any correlations among plasma levels of catecholamines, beta-thrombo-globulin (β-TG) and platelet factor 4 (PF4). In basal conditions β-TG and PF4 values in the HT patients were higher than those observed in the controls of the same age but lower than those of the PVD patients. Although the different sympathetic stimuli (90° tilting, handgrip, treadmill test, bicycle test) caused a significant increase of the plasma epinephrine (E) and norepinephrine (NE) levels, they did not modify the β-TG and PF4 levels in any of the groups studied. The platelet activation indices, therefore, regardless of the basal values, do not seem to be influenced by sympathetic stimulation.
Lack of Immune Response to Mouse IgG in Hemophilia A Patients Treated Chronically with Monoclate®, a Monoclonal Antibody Affinity Purified Factor VIII Preparation
Authors: Davis Hugh M , Brown Susan K , Nash David W , Pennetti Aniello M , Salzman Phyllis M , Schreiber Alian B , Haimovich Joseph
Published: June 2018

Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate®) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (<50 ng/ 100 I. U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgJVl and IgE anti-mouse TgG antihody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate® in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate® infusion. Data is presented demonstrating that induction of HAMA upon Monoclate® treatment does not occur. The low level of mouse IgG contained in Monoclate® appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate® in these clinical studies.
Blood Coagulation after Long Distance Running: Antithrombin III Prevents Fibrin Formation
Authors: Bärtsch Peter , Haeberli André , Werner Straub P
Published: June 2018

Physical exercise causes shortening of activated partial thromboplastin time (aPTT) and euglobulin clot lysis time. To investigate whether this activation of coagulation and fibrinolysis leads to in vivo thrombin or plasmin action after long distance running, 19 well trained male runners (36-65 years) were examined 5 to 53 min after termination of a 100 km race and 5 days later after at least 1 day without physical exercise. Compared to the control examination aPTT was decreased (30.2 ± 2.8 vs 35.3 ± 3.0 sec) and the following parameters were increased after the race: betathromboglobulin (40 ± 16 vs 23 ± 7 ng/ml), thrombin-antithrombin III (TAT) complexes (5.5 ± 3.4 vs 2.3 ± 0.7 pg/1), the fibrin(ogen) degradation products fragment E (57 ± 15 vs 35 ± 7 ng/ml) and B(3 15-42 (8.5 ± 2.5 vs 6.5 ± 2.5 ng/ml) (all p values <0.001). Platelet count, platelet factor 4, fibrinoepetide A (FPA) and haematocrit did not change significantly. Increased TAT complexes and unchanged FPA suggest that the generated thrombin was fully inactivated by antithrombin III (AT III) and did therefore not give rise to fibrin formation. The small increase of fibrin(ogen) degradation products indicates a minor in vivo activity of the fibrinolytic system. This investigation demonstrates the importance of AT III in the regulation of haemostasis in activated blood coagulation.
Characterization of a Monoclonal Antibody Specific to the Amino Terminus of the α-Chain of Human Fibrin
Authors: Mao Simon J T , Rechtin Ann E , Krstenansky John L , Jackson Richard L
Published: June 2018

A peptide, Gly-Pro-Arg-Val-Val-Glu, corresponding to the first six residues of the amino terminus of the a-chain of human fibrin (desAA-fihrin) was prepared by solid-phase peptide synthesis. The peptide was covalently linked to keyhole-limpet hemocyanin (KLH) and used as an immunogen for preparing monoclonal antibodies. A monoclonal antibody specific to the hexapeptide, but not to KLH or fibrinogen, was produced. The antibody did not bind to thrombin-mediated clots prepared from either plasma or purified fibrinogen. However, immunoreactivity was detected when fibrin (prepared from fibrinogen) was solubilized with 8 M urea. In contrast, a monoclonal antibody specific to the amino terminus (Gly-His-Arg-Pro-Leu-Asp-Lys) of the (β-chain of fibrin recognized the epitope in clots. These results indicate that thrombin cleavage of fibrinogen produces a structural change in the amino terminal domain of the α-chain that makes it inaccessible to antibody interaction. In addition, our study suggests that the potential clinical application of monoclonal antibodies to localize fibrin-rich thrombi must take into account the final structure of clots.