European Telecommunications Satellite II (EUTELSAT II)

EUTELSAT II is a regional public telecommunications system for Europe. The services which will be provided are telephone and television. The satellites will be placed at a geostationary orbit within the arcs of 6 degrees east to 19 degrees east or 26 degrees to 36 degrees east. The designed lifetime is 7 years. After separation of the satellites from the launch vehicles, telemetry, telecommand, and ranging will be performed within the S-band frequencies. After positioning of the satellite at its final geostationary orbit, the Ku-band telecommunication equipment will be activated. From this time on, all satellite control operations will be performed in Ku-band. The Deep Space Network (DSN) will support the transfer and drift orbit mission phases. The coverage will consist of the 26-m antennas at Goldstone and Canberra as prime support for the transfer and drift orbits. Maximum support will consist of a 7-day period, plus 14 days of contingency support. Information is given in tabular form for DSN support, frequency assignments, telemetry, command, and tracking support responsibility

Geostationary satellite positioning by DLR/GSOC operations and management methods

Starting with a short description of the GSOC (German Space Operations Center) and its role within the wider framework of the research institute DLR, this paper provides a review of the geostationary telecommunications satellites positioned by the GSOC. The paper then proceeds to describe the evolution of the operations and management structures and methods which have been effectively used to accomplish these missions

25 Jahre Erfahrung an der Charité

Background The creation of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with liver cirrhosis and portal hypertension is a technically demanding intervention in modern radiology. With advanced knowledge and perfection of techniques and materials the rate of periinterventional complications and technical failure decreased. Nevertheless, there is still a nonnegligible occurrence of new hepatic encephalopathy (HE) after TIPS which is associated with a reduced quality of life, an increased amount of hospitalization and poor long-term prognosis for the patient. Methods In this retrospective monocentric study collected data of all patients (n=835) who received a TIPS placement at Charité Berlin between 1993 and 2018 were filtered through the search function of our radiologic information system Centricity-RIS Software® and the patient information was extracted from patient data in paper and from the SAP System. Next to descriptive statistical analysis of the periinterventional and early-onset complications, predictive factors for the occurrence of hepatic encephalopathy after TIPS have been detected. Additionally, the Kaplan Meier Curve of survival of the patients with HE after TIPS compared to the rest of the cohort has been analyzed. Results 559 (66,9%) of 835 included patients were men. The mean age was 56 years (11-86). Most common etiologies for chronic liver disease were alcohol abuse (66,2%) and chronic hepatitis B/C infections (11,9%). Most frequent indications for TIPS placement were secondary prevention of oesophageal variceal bleeding (55,6%) and refractory ascites (22%). In 747 (89,5%) cases TIPS placement was elective. Mean MELD-Score was 13 (6-40). Within the first thirty days after TIPS placement, 170 (29,3%) patients suffered from complications. Postinterventional HE occurred in 160 [30,7%) patients (70 (13,4%) within ≤30 days post-TIPS, 90 (17,3%) later on] and was associated with increasing age (p˂ 0,001), existing chronic kidney failure (p= 0,019), high creatinine levels (p= 0,007), high MELD-Score (p= 0,004) and a big difference of pre- and post-TIPS portosystemic pressure gradient (p= 0,006). The mean survival in the HE group is over 5 years lower than in the comparison group. After 5 years more than 75% of patients in the comparison group still lived, whereas 37% of patients in the HE-group already passed. Summary This large cohort study shows that TIPS placement comes with up to 30% complication rate. Concerning the occurrence of HE, moderate decreasing of the portosystemic pressure gradient and defining severe kidney damage as a relative contraindication for TIPS placement, should be accounted for.Die Implantation eines transjugulären intrahepatischen portosystemischen Shunts (TIPS) bei Patienten mit Leberzirrhose und portaler Hypertension stellt eine technisch anspruchsvolle Intervention der modernen Radiologie dar. Mit fortschreitender Erfahrung, Verbesserung der Technik und der verwendeten Materialien sinkt die Rate des technischen Mißerfolges, sowie die Anzahl der periinterventionellen- und Spätkomplikationen. Die interventionsbedingte hepatische Enzephalopathie (HE) ist eine der häufigsten Komplikationen, die mit einer Reduktion der Lebensqualität, einer erhöhten Hospitalisierungsrate sowie einer erhöhten Mortalitätsrate für den Patienten einhergeht. Methoden In der vorliegenden retrospektiven, monozentrischen Studie wurden Daten aller Patienten (n=835), die an der Charité Berlin zwischen 1993 und 2018 einen TIPS erhalten haben, über die Suchfunktion des radiologischen Informationssystem Centricity-RIS Software® ermittelt und aus deren Patientenakten in Papierform oder dem SAP-System aus Arztbriefen und vorhandenen Patientendokumenten entnommen. Neben den Häufigkeiten der aufgetretenen periinterventionellen- und Frühkomplikationen wurden das Auftreten der HE und prädiktive Faktoren für deren Entstehen nach TIPS Anlage analysiert. Zudem erfolgte eine Überlebenszeitanalyse als Kaplan-Meier Kurve der Patienten mit aufgetretener HE nach TIPS Anlage im Vergleich zur restlichen Kohorte. Ergebnisse 559 (66,9%) der 835 eingeschlossenen Patienten waren Männer. Das mittlere Alter betrug 56 Jahre (11-86). Die häufigsten Ätiologien der Leberzirrhose waren Alkoholabusus (66,2%) und chronische Hepatitis B- oder C- Infektionen (11,9%). Die beiden meistgenannten Indikationen zur TIPS-Anlage waren die sekundäre Prävention von Ösophagusvarizenblutungen (55,6%) und der therapie-refraktäre Aszites (22%). Bei 747 (89,5%) der Patienten erfolgte die TIPS-Anlage elektiv. In den ersten 30 Tagen nach Anlage traten bei 170 (29,3%) Patienten TIPS-bezogene Komplikationen auf. Das Auftreten einer postinterventionellen HE bei 160 (30,7%) Patienten [70 (13,4%) ≤30 Tage post-TIPS, 90 (17,3%) später] war mit einem hohen Patientenalter (p˂ 0,001), vorbestehender chron. Niereninsuffizienz (p=0,019), erhöhtem Kreatininwert (p=0,007), hohem MELD-Score (p=0,004) sowie einer großen Druckdifferenz des portosystemischen Druckgradienten vor und nach TIPS-Anlage (p=0,006), assoziiert. Das mittlere Überleben in der HE-Gruppe ist um mehr als fünf Jahre niedriger als in der Vergleichsgruppe. Nach 5 Jahren lebten noch mehr als 75% der Patienten aus der Vergleichsgruppe. Zu diesem Zeitpunkt waren bereits 37% der Patienten mit HE verstorben. Zusammenfassung In dieser großen Kohortenanalyse konnte gezeigt werden, dass die TIPS-Anlage mit einer Komplikationsrate aller Komplikationen von ca. 30% einhergeht. Bezüglich des Auftretens der HE sollte eine moderate Senkung des PSDG sowie eine relative Kontraindiaktion des TIPS bei fortgeschrittener Nierenschädigung berücksichtigt werden

25 years of experience with transjugular intrahepatic portosystemic shunt (TIPS): changes in patient selection and procedural aspects

Background: TIPS is an established treatment for portal hypertension. The aim was to analyze how patient selection for TIPS implantation and procedural aspects have changed over 25 years. Routinely collected demographic, clinical, laboratory, and procedural data of 835 patients treated with TIPS in a single center were used. Time trends over the observational period from 1993 to 2018 were retrospectively analyzed. Descriptive statistical analysis was performed. Results: The most common indication for TIPS implantation has changed significantly from secondary prevention of variceal hemorrhage in the early years to treatment of recurrent ascites. During the observation period, increasingly more severely ill patients became TIPS candidates. There was little change in MELD scores over this period (in total median 13.00; IQR 10.00-18.00). The proportion of patients with Child-Pugh C cirrhosis increased. The most frequent underlying diseases in total were alcohol-related liver disease (66.5%) and viral hepatitis (11.9%). However, shares of cryptogenic liver cirrhosis, autoimmune hepatitis, and NASH increased over time. The proportion of patients post liver transplant also increased. While bare metal stents were standard in the past, use of covered stents increased. The success rate of TIPS (defined by successful implantation and a decrease in the portosystemic pressure gradient <= 12 mmHg) increased significantly over time. The total success rate according to this definition was 84.9%. Conclusion: The results of our analysis reflect technical developments in TIPS, especially in terms of stent material and gains in clinical experience, particularly regarding indications and patient selection for TIPS implantation

Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial

Background: Pirfenidone is currently approved in the EU for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) and offers a beneficial risk-benefit profile. However, there are several other, progressive fibrotic lung diseases, in which conventional anti-inflammatory therapy is not sufficiently effective and antifibrotic therapies may offer a novel treatment option. Methods/Design: We designed a study protocol for inclusion of patients with progressive fibrotic lung disease despite conventional anti-inflammatory therapy (EudraCT 2014–000861-32). The study population comprises patients with collagen-vascular disease-associated lung fibrosis (CVD-LF), fibrotic non-specific interstitial pneumonia (fNSIP), chronic hypersensitivity pneumonitis (cHP), and asbestos-related lung fibrosis (ALF). Disease progression needs to be proven by slope calculation of at least three Forced Vital Capacity (FVC) values obtained within 6–24 months prior to inclusion, documenting an annualized decline in percent predicted FVC of 5% (absolute) or more despite appropriate conventional therapy. Absolute change in percent predicted FVC from baseline - analyzed using a rank analysis of covariance (ANCOVA) model - will serve as efficacy-related primary study endpoint. Discussion: There is an urgent unmet clinical need for effective therapies for patients with a progressive fibrotic lung disease other than IPF. The current study protocol is unique with respect to selecting patients with different disease entities of lung fibrosis which have, however, essential pathophysiological characteristics in common. Moreover, by selecting patients with evidence of disease progression despite conventional therapy, the protocol ensures that a cohort of interstitial lung disease (ILD) patients with a high unmet medical need is targeted and it may allow a sufficiently high event rate for evaluation of treatment responses. Trial registration: DRKS00009822 (registration date: January 13th 2016)

Osmotic forces are not critical for Ca 2+ -induced secretion from permeabilized human neutrophils

In order to examine the role of osmotic forces in degranulation, the effects of solutes and osmolality on granule secretion were explored using both FMLP-stimulated, intact neutrophils and Ca 2+ -stimulated, permeabilized cells. We employed a HEPES-based buffer system which was supplemented with: (a) permeant (KCl or NaCI) or impermeant (Na-isethionate or choline-CI) ions, or (b) permeant (urea) or impermeant (sucrose) uncharged solutes. Intact and permeabilized cells had significantly different solute requirements for degranulation. FMLP-stimulated release from intact cells was supported by NaCI or Na-isethionate > KCl > choline-Cl or sucrose > urea. In contrast, the rank order of Ca 2+ -stimulated release from permeabilized cells was choline-C > Na-isethionate, KCl, or NaCl > sucrose > urea. Hypo-osmotic conditions caused increased levels of background granule release from both intact and permeabilized neutrophils. However, hypo-osmolality inhibited both FMLP-stimulated degranulation from intact cells and Ca 2+ -induced release from permeabilized neutrophils. While hyperosmotic conditions inhibited stimulated release from intact cells, this inhibition was much less pronounced in permeabilized cells when the granules were directly exposed to these solutions. In fact, hyperosmotic sucrose greatly enhanced Ca 2+ -induced secretion. Although isolated specific and azurophil granules showed some lytic tendencies in hypo-osmotic buffers, the overall stability of the isolated granules did not indicate that swelling alone could effect degranulation. These results suggest that degranulation in permeabilized cells is neither due to nor driven by simple osmotic forces (under resting or stimulated conditions) and emphasize differences obtained by bathing both the granules and plasma membrane (as opposed to membranes alone) in various solutes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49877/1/1041350204_ftp.pd

The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy—an open-label, prospective, randomised controlled multicenter study

Background: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. Methods: A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. Results: The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). Conclusions: There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. Clinical trial registration number: ClinicalTrials.gov identifier NCT00242606