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This article is dedicated to the memory of H.-J. Bode, J. G. Greenhill and O. Faragó for their long-standing support and participation to occultation campaigns. The work leading to these results has received funding from the European Research Council under the European Community’s H2020 2014-2020 ERC Grant Agreement n° 669416 “Lucky Star”. E.M. thanks support from Concytec-Fondecyt-PE and GA, FC-UNI for providing support during the 2012 July 18 occultation. B.S. thanks S. Para for partly supporting this research though a donation, J. P. Beaulieu for helping us accessing to the Hobart Observatory facilities and B. Warner, B. L. Gary, C. Erickson, H. Reitsema, L. Albert, P. J. Merritt, T. Hall, W. J. Romanishin, Y. J. Choi for providing data during the 2007 March 18 occultation. M.A. thanks CNPq (Grants 427700/2018-3, 310683/2017-3 and 473002/2013-2) and FAPERJ (Grant E-26/111.488/2013). J.L.O. thanks support from grant AYA2017-89637-R. P.S.S. acknowledges financial support from the European Union’s Horizon 2020 Research and Innovation Programme, under Grant Agreement no 687378, as part of the project “Small Bodies Near and Far” (SBNAF). J.L.O., R.D., P.S.S. and N.M. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709). F.B.R. acknowledges CNPq support process 309578/2017-5. G.B.R. thanks support from the grant CAPES-FAPERJ/PAPDRJ (E26/203.173/2016). J.I.B.C. acknowledges CNPq grant 308150/2016-3. R.V.M. thanks the grants: CNPq-304544/2017-5, 401903/2016-8, and Faperj: PAPDRJ-45/2013 and E-26/203.026/2015. B.M. thanks the CAPES/Cofecub-394/2016-05 grant and CAPES/Brazil – Finance Code 001. B.M. and A.R.G.J. were financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001. TRAPPIST-North is a project funded by the University of Liège, in collaboration with Cadi Ayyad University of Marrakech (Morocco). TRAPPIST-South is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant FRFC 2.5.594.09.F, with the participation of the Swiss National Science Foundation (FNS/SNSF). VSD, SPL, TRM and ULTRACAM are all supported by the STFC. K.G. acknowledges help from the team of Archenhold-Observatory, Berlin, and A.R. thanks G. Román (Granada) for help during the observation of the 2016 July 19 occultation. A.J.C.T. acknowledges support from the Spanish Ministry Project AYA2015-71718-R (including EU funds). We thank Caisey Harlingten for the repeated use of his 50 cm telescopes in San Pedro de Atacama, Chile. We thank the Italian Telescopio Nazionale Galileo (TNG), operated on the island of La Palma by the Fundación Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. L.M. acknowledges support from the Italian Minister of Instruction, University and Research (MIUR) through FFABR 2017 fund and support from the University of Rome Tor Vergata through “Mission: Sustainability 2016” fund. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clément Fillietroz-ONLUS, which is supported by the Regional Governmentof the Aosta Valley, the Town Municipality of Nus and the “Unité des Communes valdôtaines Mont-Émilius”. The research was partially funded by a 2016 “Research and Education”s grant from Fondazione CRT. We thank D.P. Hinson for his constructive and detailed comments that helped to improve this article., Context. The tenuous nitrogen (N2) atmosphere on Pluto undergoes strong seasonal effects due to high obliquity and orbital eccentricity, and has recently (July 2015) been observed by the New Horizons spacecraft. Aims. The main goals of this study are (i) to construct a well calibrated record of the seasonal evolution of surface pressure on Pluto and (ii) to constrain the structure of the lower atmosphere using a central flash observed in 2015. Methods. Eleven stellar occultations by Pluto observed between 2002 and 2016 are used to retrieve atmospheric profiles (density, pressure, temperature) between altitude levels of ~5 and ~380 km (i.e. pressures from ~ 10 μbar to 10 nbar). Results. (i) Pressure has suffered a monotonic increase from 1988 to 2016, that is compared to a seasonal volatile transport model, from which tight constraints on a combination of albedo and emissivity of N2 ice are derived. (ii) A central flash observed on 2015 June 29 is consistent with New Horizons REX profiles, provided that (a) large diurnal temperature variations (not expected by current models) occur over Sputnik Planitia; and/or (b) hazes with tangential optical depth of ~0.3 are present at 4–7 km altitude levels; and/or (c) the nominal REX density values are overestimated by an implausibly large factor of ~20%; and/or (d) higher terrains block part of the flash in the Charon facing hemisphere., European Research Council under the European Community’s H2020 2014-2020 ERC Grant Agreement n° 669416 “Lucky Star”, Grants 427700/2018-3, 310683/2017-3 and 473002/2013-2) and FAPERJ (Grant E-26/111.488/2013), Grant AYA2017-89637-R. P.S.S. acknowledges financial support from the European Union’s Horizon 2020 Research and Innovation Programme, under Grant Agreement no 687378, as part of the project “Small Bodies Near and Far” (SBNAF), Financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709), Support process 309578/2017-5. G.B.R. thanks support from the grant CAPES-FAPERJ/PAPDRJ (E26/203.173/2016). J.I.B.C. acknowledges CNPq grant 308150/2016-3. R.V.M. thanks the grants: CNPq-304544/2017-5, 401903/2016-8, and Faperj: PAPDRJ-45/2013 and E-26/203.026/2015. B.M. thanks the CAPES/Cofecub-394/2016-05 grant and CAPES/Brazil – Finance Code 001., Grant FRFC 2.5.594.09.F, with the participation of the Swiss National Science Foundation (FNS/SNSF), Support from the Spanish Ministry Project AYA2015-71718-R (including EU funds), Support from the Italian Minister of Instruction, University and Research (MIUR) through FFABR 2017 fund and support from the University of Rome Tor Vergata through “Mission: Sustainability 2016” fund

Altere Patienten mit kardiovaskularen Erkrankungen sind regelmasig antikoaguliert, was bei der Vorbereitung und Durchfuhrung operativer Eingriffe berucksichtigt werden muss. Atiologie, Diagnostik und klinisches Management ausgewahlter angeborener und erworbener Gerinnungsstorungen mit erhohter Blutungs- und Thromboseneigung werden beschrieben. Ergebnisse ausgewahlter klinischer Studien und Leitlinien sowie Expertenempfehlungen werden dargestellt. Bei Alteren finden sich neben angeborenen Hamostasedefekten sehr viel haufiger erworbene Gerinnungsstorungen durch die Einnahme von Medikamenten zur Behandlung chronischer Schmerzen oder kardiovaskularer Erkrankungen. Selten findet sich auch eine erworbene, autoimmune Hemmkorper-H amophilie mit schwerwiegender Blutungsneigung. Altere Patienten haben zudem ein deutlich erhohtes Risiko fur die Entwicklung venoser und arterieller Thromboembolien. Vor elektiven Eingriffen sollte der praoperative Ausschluss einer erhohten Blutungsneigung durch die Kombination von Anamnese, klinischer Untersuchung und zielgerichteter Labordiagnostik erfolgen. Dabei kommt der korrekten Abklarung auffalliger Befunde des Laborscreenings eine besondere Bedeutung zu, insbesondere im Falle einer pathologisch verlangerten aktivierten partiellen Thromboplastinzeit (aPTT). Das Management alterer und haufig antikoagulierter Patienten muss ausreichend lange vor der Operation beginnen und auch die peri- und postoperative Phase einschliesen. Bei Risikopatienten sollten hamostaseologisch qualifizierte Arzte in die Behandlungsplanung eingebunden werden. Zum sicheren Management der Prophylaxe venoser Thromboembolien stellt die Umsetzung einschlagiger klinischer Leitlinien nicht nur fur Patienten vor einer Operation eine sehr sinnvolle Masnahme dar.

Background: Growth and differentiation factor 15 (GDF-15) is a remote member of the TGF-β protein family with low to absent expression in healthy tissue. During pregnancy GDF-15 is secreted in high amounts by placenta contributing to feto-maternal tolerance. Similarly, GDF-15 expression is upregulated following tissue injury serving as a key inhibitor of excessive and disruptive immune infiltration. Importantly, various major tumor types secrete high levels of GDF-15 correlating with poor prognosis and reduced overall survival. Methods: In a flow-adhesion assay different immune cell subsets pre-treated +/- GDF-15 were perfused over an activated layer of endothelial cells or recombinant adhesion molecules. Adhesion and transmigration processes were monitored by live imaging microscopy. Impact of a proprietary GDF-15 neutralizing antibody (CTL-002) regarding T cell trafficking were analyzed. In a humanized (CD34+-HPSC engrafted) PDX mouse model inoculated with the PD-L1hi and GDF-15 secreting human melanoma tumor cell line HV18-MK T cell infiltration was analysed +/- CTL-002 by FACS. Results: Adhesion of T cells to the endothelial cell layer was significantly impaired by addition of GDF-15. Among T-cell subsets CD8+ T-cells were most affected while adhesion of other immune cells was not reduced. Inhibitory effects of GDF-15 on CD8+ T-cell adhesion were comparable to potent blockade of LFA-1 by TS1/18 antibody and could be rescued by the anti-GDF-15 antibody CTL-002. In vivo, neutralization of GDF-15 in HV18-MK melanoma-bearing humanized mice by CTL-002 resulted in a strong increase of tumor infiltrating leukocyte numbers. Subset analysis revealed an overproportional enrichment of T-cells, especially CD8+-T cells. Conclusion: Our in vitro and in vivo data show that elevated GDF-15 levels block T-cell infiltration into the tumor tissue. Neutralizing GDF-15 with a proprietary antibody (CTL-002) restored the ability of T cells (especially CD8+-T-cells) to extravasate blood vessels and enter tumor tissue both in vitro and in vivo. As it is known that presence of tumor-infiltrating lymphocytes correlates with better patient outcomes in a multitude of cancers and is a predictor of response to checkpoint inhibitors, high levels of GDF-15 in the tumor may contribute to failure of immunotherapies and poor overall survival. Neutralization of GDF-15 could be a new and promising approach to increase response rates of immunotherapies and increase overall survival of cancer patients. Citation Format: Markus Haake, Neha Vashist, Sabrina Genssler, Kristin H. Eichler, Birgitt Fischer, Jessica Kammer, Paula S. Romer, Manfred Rudiger, Eugen Leo, Falk Nimmerjahn, Christine Schuberth-Wagner, Jorg Wischhusen. Tumor-derived GDF-15 suppresses T-lymphocyte recruitment to the tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5597.

A new airborne tandem measurement platform for cloud-radiation interaction studies is introduced in this paper. It consists of a Learjet 35A research aircraft and the AIRcraft TOwed Sensor Shuttle (AIRTOSS), which is an instrumented drag-body towed by the Learjet. Currently, the AIRTOSS is instrumented with a Cloud Imaging Probe (CIP) for measuring cloud microphysical properties and an Inertial Navigation System (INS) for measurements of flight attitudes. The cable dragging AIRTOSS can be as long as four kilometres. Thus, truly collocated measurements in two altitudes above, in, and below clouds can be obtained. Results from first test flights with Learjet and AIRTOSS are reported here. The flights were performed from Hohn Airport, Germany. Specific manoeuvres were flown to test the aerodynamic behaviour of the drag-body and to investigate the suitability of AIRTOSS for high-precision irradiance measurements which require a stable flight attitude of AIRTOSS. The flight attitude data show that AIRTOSS is sensitive to several flight manoeuvres such as curves, altitude and airspeed changes, and also to changes of towing cable length. The effects of these manoeuvres on the attitude angles of AIRTOSS have been quantified. Maximum roll angle deviations were observed during curve flight. Even small changes in heading can lead to high roll angles (one degree change in heading causes a change in roll angle of about eight degrees). The pitch angle varies during climb or dive periods, extending or retracting of towing cable, acceleration or deceleration, and even when flying at too low or too high true airspeed depending on altitude. Values of pitch angle between −5° (dive) and 8° (climb and retracting towing cable) have been observed. While change in attitude is not problematic for cloud particle property measurements it is for radiation measurements. Here, the deviation from the horizontal should be no more than 3° to avoid large errors. When keeping the above mentioned flight parameters constant, sufficiently stable flight conditions can be maintained to perform high-quality irradiance measurements with AIRTOSS in future experiments. During this test campaign also observations of cloud microphysical data as for example droplet number concentrations and size distributions with the AIRTOSS in stratocumulus clouds were performed to prove the compliance with scientific needs. Simultaneous radiation measurements of the clouds have been made. The measurements of internal operational data of AIRTOSS as well as the first atmospheric data demonstrate the suitability of this tandem platform for detailed cloud microphysics and radiation interaction studies.

Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients. Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.

Vorgestellt wird eine 71-jahrige Patientin mit ekzematosen, therapierefraktaren Hautveranderungen beider Mamillae seit 2,5 Jahren. Trotz intensiver gynakologisch/radiologischer Abklarung konnten keine Auffalligkeiten festgestellt werden. Durch die operative Versorgung des beidseits durch Biopsie diagnostizierten M. Paget wurden jedoch duktale Karzinome (DCIS) bestatigt. Insbesondere bei therapierefraktaren Hautbefunden der Mamille sollte die Indikation zur Biopsie groszugig gestellt werden. Bestatigt sich die Verdachtsdiagnose M. Paget, ist die operative Versorgung auch zum Ausschluss ursachlicher duktaler Karzinome unverzichtbar.

Elderly patients often suffer from cardiovascular diseases and are treated with anticoagulation medications, which must be taken into consideration when planning elective surgery.The etiology, diagnostic work-up and clinical management of selected inherited and acquired hemophilic and thrombophilic coagulation disorders are described.Data from clinical studies, current guidelines and expert opinions are discussed.Beside inherited hemophilic coagulation defects, elderly patients very frequently show an acquired bleeding tendency caused by the intake of analgesic drugs or long-term medication due to cardiovascular diseases. In rare cases, elderly patients can develop acquired hemophilia caused by autoantibodies to coagulation factors resulting in a severe bleeding disorder. Moreover, elderly patients have an increased risk to develop venous or arterial thrombotic events. Prior to surgery a relevant bleeding tendency should be excluded by the combination of medical history, clinical investigation and screening of laboratory parameters. If laboratory parameters are outside the normal range, e.g. a prolonged activated partial thromboplastin time (aPTT), the reasons must be clarified prior to an elective surgery.The clinical management of elderly patients under anticoagulation treatment should start early and must also cover the post-surgery period. When planning treatment for patients at risk, a physician qualified in clinical hemostaseology should be consulted. For the management of thrombosis prophylaxis, the implementation of clinical guidelines is a valuable measure.

Objective: Interventional cardiovascular implants in young children are often associated with midterm morbidities such vessel narrowing and thrombosis. The aim of our study was to develop coating surface with improved bio- and hemo-compatible qualities to overcome several blood and tissue material interactions. Methods: The novel surfaces were developed using variant coating Methods as chemical vapor deposition (CVD) and wet-chemistry process as dip-coating. As follows, several surface analyses have been performed like wetting angle measurements, surface morphology, surface roughness and composition. To test the hemo-compatibility, an ex vivo circulation model using miniaturized centrifugal pump with a maximal load volume of 16mL (Medos, Germany) was established. Different surface specimens with a diameter of 12mm were loaded on a special developed holder and inserted into the circulation system. All experiments were performed by using the whole blood of a single healthy donor, in a flow rate of 1,500mL/min for a duration of 10 minutes. After perfusion, the morphology of thrombocytes was observed by scanning electron microscopy (SEM) and adhesion number was quantitatively counted. For cytotoxicity studies, human cardiomyocytes (HCM) were cultured with the extract from each surface and LDH assay was performed to determine the membrane disintegration level and WST-1 assay to detect cells proliferation. Results: The new developed surfaces showed a super hydrophobicity toward water, blood and proteins. Morphology and roughness are always identical, while the coatings were stable. The ultra-hydrophobic surface is highly cyto- and hemo-compatible. In comparison to control, platelets adhesion and activation is significantly reduced. Additionally, there is no cytotoxic effect on the HCM (p< 0.5). Conclusion: This new approach represents an ultra-hydrophobic surface, which may potentially serve as coating for cardiovascular implants such stents and heart valves for the use in pediatric patients.

A survey-based, cost–benefit analysis was performed comparing blood screening strategies with vaccination strategies for the reduction of transfusion transmission of HBV. 231 whole blood donors and 126 apheresis donors were eligible and completed a questionnaire detailing their donation habits. The cost–benefit analysis included current mandatory HBV testing (HbsAg + anti-Hbc, A1), A1 with additional nucleic acid testing (NAT) for minipool (A2) or individual donation testing (A3), as well as HBV vaccination strategies using time-dependant (B1) or titre dependent booster vaccination solely (B2), or B2 in addition to current mandatory testing procedures (B3). Different cost models were applied using a 5% rate of discount. Absolute costs for current mandatory testing procedures (A1) over 20 years in Germany were €1009 million. Additional NAT would lead to incremental costs of 43% (A2) or 339% (A3), respectively. Vaccination strategies B1 and B2 showed cost-reductions relative to A1 of 30% and 14%, respectively. The number of remaining HBV infections could be reduced from 360 (for A1) to 13, using vaccination, compared with 144 or 105 remaining infections for A2 or A3, respectively. Absolute cost per prevented infection is similar (€2.0 million) for A2 and B3. HBV vaccination offers the near-elimination of transfusion infections while representing a potential cost-reduction.

Phlebothrombosen und Lungenembolien sind auch heutzutage gefurchtete perioperative Komplikationen und verursachen in Europa und den USA ca. 300.000–500.000 Todesfalle/Jahr. Das hochste Thromboembolierisiko besteht bei Knie- und Huftoperationen. Operations- und Anasthesieverfahren sowie eine Vielzahl von Triggermechanismen (expositionelle und dispositionelle Risikofaktoren einschlieslich laboranalytisch messbarer Thrombophilien) nehmen Einfluss auf das Thromboserisiko. Neben der Anwendung physikalischer Masnahmen konnte durch die Weiterentwicklung antithrombotisch wirksamer Medikamente die Thromboserate bei Hochrisikopatienten signifikant reduziert werden. Niedermolekulare Heparine haben dabei einen festen Stellenwert in Klinik und Praxis. Aber auch eine aPTT-adjustierte perioperative Vorgehensweise hat ihre Berechtigung. Die Kenntnis einer Thrombophilie hat fur den Chirurgen eine untergeordnete Bedeutung, zumal derzeit auch allgemein verbindliche Empfehlungen fur die Behandlung von Patienten mit Thrombophilie nicht existieren. Von groserer Bedeutung hingegen ist die Erhebung einer gezielten Eigen- und Familienanamnese, aus der stattgehabte thrombotische Komplikationen oder innerfamiliare Haufungen abgeleitet werden konnen. Mit der Entdeckung des Pentasaccharids konnte die antithrombotische Effizienz weiter verbessert werden. In nationalen wie internationalen Leitlinien haben die niedermolekularen Heparine, aber auch Fondaparinux mittlerweile einen festen Platz, wohingegen neuere oral verfugbare Anti-IIa- bzw. Anti-Xa-Inhibitoren derzeit keine Berucksichtigung finden. Ob und inwieweit welcher Patient (mit/ohne thrombophile Disposition) unter welchen Bedingungen von welchem Medikament im Rahmen einer AK-Prophylaxe uber welchen Zeitraum am meisten profitiert, wird Gegenstand weiterer Prufung sein. Grundsatzlich mussen aber das Alter des Patienten, neben Nieren- und Leberfunktionswerten sowie mogliche Medikamenteninteraktionen bei der Wahl des jeweiligen Antithrombotikums Berucksichtigung finden. Auch eine im Einzelfall zu berucksichtigende Verlangerung der Immobilisationsprophylaxe kann Kumulationsrisiken bedingen, wie z. B. die Induktion einer Heparin-induzierten Thrombozytopenie, deren Risiko mit der Dauer der Exposition des „auslosenden Agens“ wachst.

In a numerical study, influences of relative humidity (RH) on aerosol optical properties and direct radiative forcing in the surface boundary layer at Xinken (XK) in Pearl River Delta of China are investigated based on the observed particle hygroscopic growth ( f g ( D p , RH ) ) and the relevant aerosol physical and chemical properties. The model is validated by comparing the simulated ambient extinction coefficients with those measured by a Raman LIDAR. At 550 nm, the scattering coefficient increases with a factor of 1.54 and 2.31 at a RH increase from 30% to 80% and 90%, respectively. This ratio is mainly controlled by f g , and generally increases with increasing wavelength and decreases with increasing particle effective diameter. From RH 30% to 90%, the average single scattering albedo ( ω 0 ) changes from 0.77 to 0.88, 0.91 to 0.97, and 0.86 to 0.94 for internal, respectively, external mixtures, and the retrieved mixing state of the elemental carbon (EC) at XK. The assumption that the absorption coefficient does not change upon humidification alone can introduce an overestimation of ω 0 of 0.02 ( ∼ 5 % ) at RH 90% for an internal mixture. However, accounting for the EC mixing state at XK, this error is only about 0.3%. The mean upscatter fraction ( β ¯ ) is evaluated as 0.233 at RH 30% with a 30% decrease to 0.191 at RH 90%. The estimation of aerosol direct radiative forcing ( Δ F R ) in the surface boundary layer at XK strongly depends on RH and the EC mixing state. The critical ω 0 at XK is estimated to be about 0.77–0.80 at 550 nm. Assuming an internal or coated mixture of EC, no pronounced Δ F R is observed when RH 60 % , whereas a cooling effect arises while RH > 60 % . Under the actual EC mixing conditions at XK, the effect of Δ F R is cooling. Over 40% of this cooling effect is contributed by water at RH 80% and Δ F R at RH 90% exceeds that at RH 30% by about a factor of 2.7.

During the “Program of Regional Integrated Experiments of Air Quality over Pearl River Delta 2004 (PRIDE-PRD2004)” hygroscopic properties of particles in the diameter range 22 nm to 10 μ m were determined. For that purpose, a Humidifying Differential Mobility Particle Sizer (H-DMPS) and a Micro-Orifice Uniform Deposition Impactor (MOUDI) were operated. The derived size-dependent particle hygroscopic growth factors were interpolated to ambient relative humidity (RH) and used to calculate the particle number size distributions (PNSDs) at ambient conditions. A comparison between the modeled particle extinction coefficients ( σ ext , Mie ) and those observed with a Raman lidar was made. It is shown that the particle extinction coefficient ( σ ext ) at ambient RH can be properly estimated with Mie-model calculations based on the in situ physico-chemical measurements of dry and humidified PNSD and chemical composition.

Aerosol optical properties (AOPs) of sub- 10 μ m particles under dry conditions (relative humidity (RH) 20 % ) were investigated at Xinken in Pearl River Delta of China from 4 October to 5 November 2004. Severe aerosol optical pollution has been found characterized by strongly light-absorbing particles. At 550 nm, the magnitude of the light scattering ( 333 ± 138 Mm - 1 ) and absorption ( 70 ± 42 Mm - 1 ), limited visual range ( 5.3 ± 2.5 km ), and low single scattering albedo ( 0.83 ± 0.05 ) show Xinken to be comparable to the most polluted urban cores rather than even a polluted rural site. Other presented AOPs include hemispheric backscattering fraction ( 11 ± 1 % ) and asymmetry parameter ( 0.67 ± 0.01 ) at 550 nm, and Angstrom exponent ( a ˚ 450 / 700 = 1.6 ± 0.15 ). Systematic relationships exist among the various AOPs. Their diurnal variations cannot be solely explained with the development of atmospheric boundary layer, but also obviously influenced by local wind patterns, variation of sources, photochemistry and nighttime heterogeneous chemistry. The fractional contributions to extinction, scattering and absorption ( f ep ; sp ; ap ) due to sub-aerosol-populations and individual chemical compounds are derived by the Mie simulations. The sub- 1 μ m particles contribute more than 90% of the particle extinction ( σ ep , 550 nm ). Under dry conditions, f ep of non-sea-salt sulfate, particulate organic matter, elemental carbon (EC) and residual are about 44%, 17%, 17% and 15%, respectively. However, the water uptake of particles can contribute 50–60% to σ ep , 550 nm at RH 90%. So in the ambient atmosphere, sulfate, carbonaceous material and water all play very important roles, concerning the visibility impairment at Xinken. The respective mass extinction, scattering and absorption efficiencies ( α ep ; sp ; ap ) are mostly consistent with previously reported values for the polluted area. α ap , EC , 550 nm for sub- 1 μ m and sub- 10 μ m ranges are 9.3 ± 1.4 and 7.2 ± 1.0 m 2 g - 1 , respectively. Our results imply a higher α ap , EC for more internally mixed EC under the atmospheric conditions present at Xinken.

Results are reported from a ground-based measurement campaign conducted in a highly polluted region in southeast of China in October–November 2004. The experiment focused on absorbing aerosol particles and their effects on the solar radiation field and local meteorology. A Raman lidar in conjunction with Sun photometer data measured profiles of particle extinction; ground-based in situ data of aerosol optical properties were collected by nephelometer and absorption photometer. Exceptionally high values of aerosol optical depth of up to 1.5 were observed. The measurements were input to a radiative transfer model, which simulated high solar radiative forcing values for the aerosol particles of up to - 160 W m - 2 at the ground (daily average) for the observed particle single-scattering albedo of 0.85. Maximum solar heating rates of 7– 8 K day - 1 were simulated at the top of the aerosol layer. The radiative simulations were used to drive a dynamic model of the planetary boundary layer (PBL). With this model the temporal course of the height of the PBL was simulated and compared with respective lidar data. The results show that the height of the PBL is significantly decreased due to the warming of the aerosol particles at the top of the PBL. In this way, the stabilizing effect of absorbing aerosol particles within the PBL was confirmed by a combination of experimental and modeling means.

Local laser-induced oxidation of thin titanium films on glass is shown to be self-limiting due to a decrease in the absorptivity during the reaction. Taking advantage of this confinement, stable writing of transparent oxide line structures narrower than the diffraction-limited focused spot of a continuous wave Ar ion laser (500 nm) has been accomplished. The greatest optical contrast (1:10) with the highest resolution down to 165 nm was observed if the film thickness is of the order of the light absorption length in the metal.

Verschleiß- und Korrosionsschutzschichten auf Bauteilen und Werkzeugen lassen sich mit hoher Präzision durch Laser-Pulver-Auftragschweißen herstellen. Die zur Erzielung hochwertiger Schichten geeigneten Prozessparameter hängen empfindlich von der Werkstückgeometrie und den Materialeigenschaften ab und sind derzeit noch durch aufwändige Tests experimentell zu ermitteln. Ziel der Simulation sind Kosteneinsparungen durch rechnerische Vorausbestimmung und Optimierung von Prozessfenstern auf einer "virtuellen Anlage".

Der Einsatz von zellularen Blutkomponenten und Blutprodukte aus Plasmaspenden ist aus der heutigen Medizin nicht mehr wegzudenken. Jahrlich werden in der Bundesrepublik Deutschland etwa 4,2 Mio. Blutspenden von freiwilligen Blutspendern entgegengenommen. Trotz intensiver Aufklarung und Werbung sind Blutpraparate insbesondere in den Urlaubsmonaten knapp. Die begrenzten Ressourcen und die mit der Ubertragung von Fremdblut verbundenen Risiken verpflichten zu einem rationalen Umgang mit Blutpraparaten. Neben den Anwendungsgebieten von Erythrozyten- und Thrombozytenkonzentraten werden im Folgenden die nur in sehr begrenztem Umfang verfugbaren Granulozyten- und Lymphozytenpraparate vorgestellt.

Thin ceramic layers with a gradient in the grain size and the pore size distribution were prepared by centrifugal deposition fron diluted suspensions with a very low solid content and a multimodal particle size distribution. Besides drying and sintering of the sediments, a main problem is the detection of the gradient which can be expected to appear owing to the settling behaviour of the particles during centrifugation. For this reason, the layers were characterized by quantitative image analysis, atomic force microscopy (AFM) and grazing incidence small angle x-ray scattering (GISAXS).

We report on three alternative approaches to laser-supported sub-micro- and nanopatterning of ultrathin films. The inherent non-linearities of direct writing techniques can be used to fabricate structures far below the optical resolution limit. Due to the non-linear dependence of light absorption and reaction rate on film thickness and temperature (a) the lateral self-limitation of the oxidation reaction in ultrathin titanium films on a transparent heat insulating substrate in air can occur. The polarization of sharp conducting tips results in (b) near-field enhancement of the optical field in nanometer regions that allows diminishing of the effective size of the radiation source. The third approach (c) is based on the nanometer-period pattern transfer from a biomolecular template to a Pt/C overlayer deposited by cross-beam pulsed laser deposition.

Background: Shortly after the gel test was introduced into routine immunohaemato-logy, an increased percentage of patients were reported to show a positive auto-control in the indirect antiglobulin test (IAT) of uncertain significance as the direct antiglobulin test (DAT) in the tube technique was negative. Materials and Methods: In our study 13,280 randomized patient blood samples were screened and additional investigations carried out including an analysis of patient histories in the 97 blood samples that were auto-control positive in the gel test. Results: In 87.4%, a re-testing with polyspecific antiglobulin serum (83.2% with anti-IgG) showed positive results in contrast to only 52.9% re-tested by the tube test. Neither nonspecificity nor cold agglutinins were significant. None of the patients examined showed any signs of haemolysis exept for one with pernicious anaemia. We concluded that the increased number of positive auto-controls and DATs is due to the greater sensitivity of the gel test and thus the detection of minute quantities of specific cell-bound IgG molecules, i. e. warm auto-antibodies or drug-induced antibodies. Conclusion: Prior to transfusion, a positive result should be confirmed by a tube DAT. If this test is negative and there is no history of a previous transfusion or of haemolysis, the transfusion should not be delayed by carrying out further time-consuming investigations.Schlüsselwòrter

The collection of related allogenic cord blood is gaining increasing importance in families with one child affected by haematopoietic disease. Within a family, there is only a 25% chance of a full HLA match between siblings. 50% of all collected cord blood samples cannot be used because of poor quality. Because of this, the determination of HLA type is useful for planning the collection of related allogenic cord blood transplants. We studied whether HLA typing is possible during late pregnancy if amniocentesis has not been performed during the first trimester. HLA -A, -B and -DRB loci were detected in amniotic fluid, as well as in corresponding cord blood and maternal blood using PCR-SSP. For the first time, HLA typing was performed from uncultured amniocytes. Unambiguous results were obtained from all samples. Fetal HLA-genotype in amniotic fluid was confirmed by typing results from corresponding cord blood. HLA typing of uncultured amniocytes during late pregnancy is a reliable and fast method. For the first time, prenatal HLA typing by amniocentesis after week 38 of gestation is possible in less than 8 h and without fetal risk.

Recombinant factor VIIa is indicated for treatment of bleeding episodes in patients with haemophilia A or B with inhibitors; in FVII deficiency and in Glanzmann's thrombasthenia. The aim of the study reported here was to compare the pharmacokinetic profiles between two formulations of rFVIIa that are produced in two different cell lines and media: Chinese hamster ovary cells cultured in a serum-free medium (CHO-rFVIIa) and baby hamster kidney cells cultured in a non-human serum-based medium (BHK-rFVIIa). Two clinical trials were performed; one in healthy subjects and the other in patients with congenital haemophilia A or B, with or without inhibitors. Subjects were recruited into a two-way crossover trial and were randomized to receive a dose of CHO-rFVIIa and BHK-rFVIIa. Healthy subjects received one dose of 90 μg CHO-rFVIIa kg(-1) bodyweight (bw) in the newly developed room-temperature stable rFVIIa formulation and one dose of 90 μg BHK-rFVIIa kg(-1) bw, in the original rFVIIa formulation. Patients with haemophilia received one dose of 270 μg CHO-rFVIIa kg(-1) and one dose of 270 μg BHK-rFVIIa kg(-1), both in the room-temperature stable formulation. The trials showed higher FVII activity levels [higher area under the plasma concentration-time curve (AUC)] following administration of CHO-rFVIIa than after BHK-rFVIIa. Therefore, bioequivalence could not be established. The difference in FVII activity levels is believed to be a result of different glycosylation patterns between the two products. Neither the use of CHO-rFVIIa nor the use of one single dose of 270 μg kg(-1) of the newly developed room-temperature stable rFVIIa raised any safety concerns.

BACKGROUND Due to the ageing population, blood donation by the elderly is necessary to maintain blood supply. We initiated a prospective study, to assess whether there is an increased risk of donor reactions in elderly donors. STUDY DESIGN AND METHODS In this prospective study, regular donors aged from 66 to 68 and 69 to 71 years were invited to continue blood donation on mobile collection sites of the German Red Cross Blood Service West. A control group (50-52 years) was established. Admission of donors in all groups followed the German national guidelines for blood donation. Donor deferrals and all kinds of donor reactions during donation (on-site) and in the 48 h following donation (off-site) were monitored. RESULTS A total of 64 260 valid cases were entered in the study. Donor deferrals increased with age from 1·12% in the control group up to 8·74 in female donors aged 69-71 years. Adverse reactions to blood donation were rare with an overall reaction rate of 0·63% (0·05% on-site; 0·58% off-site). Off-site reactions significantly decreased with increasing age. The relative risk (RR) for adverse reactions in elderly donors compared to the control group (50-52 years) was slightly increased for on-site reactions in the 69- to 71-year-old donors (RR 1·0309; 95% CI 1·0292-1·0325). In all other comparisons, the RR for adverse reactions was distinctively lower in elderly donors (RR 0·3785 - 0·7778). CONCLUSIONS Our data confirm that elderly regular blood donors may safely continue blood donation at least to the age of 71. Based on these data, we increased the upper age limit.

Airborne measurements of spectral upwelling radiances (350A¢Â�Â�2200 nm) reflected by cirrus using the Spectral Modular Airborne Radiation measurement sysTem (SMART)-Albedometer were made over land and water surfaces. Based on these data, cloud optical thickness tau and effective radius Reff of the observed cirrus were retrieved. By using different crystal shape assumptions (hexagonal plates, solid and hollow columns, rough aggregates, planar and spatial rosettes, ice spheres, and a mixture of particle habits) in the retrieval, the influence of crystal shape on the retrieved tau and Reff was evaluated. With relative differences of up to 70%, the influence of particle habit on t is larger than on Reff (up to 20% differences). Retrieved tau values agreed with values derived from concurrent lidar measurements within the measurement uncertainties.

Venous thrombosis and pulmonary embolisms are currently associated with high mortality rates in Europe as well as in the United States (mortality rate300,000-500,000/year). The highest risk is attributed to orthopedic surgery. Besides the use of antithrombotic agents, surgical and anesthesiological procedures as well as a multitude of trigger mechanisms, many thrombophilic risk conditions have to be considered. The incidence of thrombotic complications could be continuously reduced by the improvement of different antithrombotic strategies and use of drugs. According to national and international guidelines low molecular weight heparins and fondaparinux (besides aPTT adjusted strategies by using unfractionated heparin) are mainly indicated in high risk patients undergoing hip and knee surgery.The use of newly developed anti-IIa and anti-Xa inhibitors (e.g. dabigatran etexilate, rivaroxaban) is not yet established in guidelines. The discovery of pentasaccharide has further improved the antithrombotic efficiency, but it is still unknown how to manage patients with thrombophilia. Otherwise the knowledge of thrombophilia is not mandatory to know how to manage high risk patients. In contrast information on a history of thrombotic complications as well as indications gained from the family history are of great importance. Whether and to what extent, which patients with or without thrombophilic disposition, under which conditions from which medication within an anti-coagulation prophylaxis profit most over which time period, will be of future interest. Fundamentally, the age of the patient as well as liver and kidney function values and possible interactions between medications must be taken into consideration for selection of individual anti-thrombotic drugs. Even prolongation of medical immobilization prophylaxis can lead to accumulative risks, such as heparin-induced thrombocytopenia, the risk of which grows with increased exposition to the triggering agent.

Haemorrhagic disorders must be excluded prior to any operation or other invasive procedure that has the potential to involve serious bleeding. When assessing the individual risk of bleeding, screening tests of hemostasis must be combined with the patient's clinical history and symptoms, and any history of bleeding must be explored under direct medical supervision using a standardized questionnaire. However, this bleeding history is neither very specific, nor is it particularly sensitive. Screening tests that have been found to be useful include platelet count, activated partial thrombo plastin time (aPTT), prothrombin time (PT) and clottable fibrinogen. No reliable, sensitive and specific screening test is however available today to screen for platelet dysfunction or von Willebrand disease. A specialized coagulation laboratory should be involved when the bleeding history or laboratory screening indicate a potential haemorrhagic disorder.

Morphological properties of thermally structurized polyacrylnitril (TSPAN) have been studied with regard to their electrochemical properties in the nm range in order to optimize the process of pyrolysis generating such polymers.

[1] Particle size and absorption properties have been determined from combined one-wavelength Raman lidar and Sun photometer measurements in the Pearl River Delta (South China) in October 2004, and in Beijing (North China) in January 2005. Particle effective radius varied around 0.24 μm in the south of China. Aerosols were strongly light absorbing throughout the continental haze layers. The mean imaginary part was around 0.02i and the single-scattering albedo was as low as 0.75 at 532 nm wavelength. Similar aerosol properties were found over Beijing.

Received 29 November 2005; revised 28 April 2006; accepted 5 June 2006; published 21 October 2006. [1] The aerosol mixing state was investigated with an optical closure study at Xinken, Pearl River Delta of China in 2004. On the basis of in situ aerosol microphysical and chemical measurements and a two-component aerosol optical model an internal consistency algorithm was developed to model the mass ratio (r) of externally mixed elemental carbon (EC) to total EC, which minimized the discrepancies between measured and calculated optical properties. The rest of EC was assumed to be internally mixed. A time series of r was retrieved. Good agreement between model and observation was found, on the order of ±15% for total/back scattering coefficients and ±10% for absorption coefficient. The EC mixing state was strongly dependent on the local wind patterns. When north/northeasterly winds prevailed, the air came from the urban and industrial areas of mainland China, and EC was mainly externally mixed with an average r of 85 ± 12%. When the airflow was controlled by a weak local wind system, the mixing state showed a pronounced diurnal variation. During daytime the wind speed was nearly zero. This favored the increase of local pollution, and the average r was about 95%. However, during nighttime the EC mixing state transformed to be internally mixed apparently with an average r of 53 ± 15%, which can be explained by a more aged air mass. The south/ southeasterlywindscomingfromtheseawerefoundtohavethemostimportanteffectonthe transformation of EC mixing state in the night, but fairly rapid local aging processing was also observed. The uncertainties of the model were explored by a Monte Carlo simulation.

cw‐laser‐induced local oxidation of ultrathin (3–60 nm) titanium films on glass in air is studied. It is shown, that the brightening of the films upon through‐oxidation forms a negative feedback to this highly nonlinear process. It offers the possibility of stable writing of oxide line structures narrower than the diffraction limited focused laser spot. The optimum metal film thickness is of the order of the light absorption length in the metal. Transparent isolated oxide lines and gratings with periods down to 250 nm and line width down to 165 nm were recorded in 6–15 nm thick Ti films on glass by using the radiation of the Ar ion laser (λ=488, 514 nm).