Towards climate-neutral aviation: Assessment of maintenance requirements for airborne hydrogen storage and distribution systems

Airlines are faced with the challenge of reducing their environmental footprint in an effort to push for climate-neutral initiatives that comply with international regulations. In the past, the aviation industry has followed the approach of incremental improvement of fuel efficiency while simultaneously experiencing significant growth in annual air traffic. With the increase in air traffic negating any reduction in Greenhouse Gas (GHG) emissions, more disruptive technologies such as hydrogen-based onboard power generation are required to reduce the environmental impact of airline operations. However, despite initial euphoria and first conceptual studies for hydrogen-powered aircraft several decades ago, there still has been no mass adoption to this day. Besides the challenges of a suitable ground infrastructure, this can partly be attributed to uncertainties with the associated maintenance requirements and the expected operating costs to demonstrate the economic viability of this technology. With this study, we address this knowledge gap by estimating changes towards scheduled maintenance activities for an airborne hydrogen storage and distribution system. In particular, we develop a detailed system design for a hydrogen-powered, fuel-cell-based auxiliary power generation and perform a comparative analysis with an Airbus A320 legacy system. That analysis allows us to (a) identify changes for the expected maintenance effort to enhance subsequent techno-economic assessments, (b) identify implications of specific design assumptions with corresponding maintenance activities while ensuring regulatory compliance and (c) describe the impact on the resulting task execution. The thoroughly examined interactions between system design and subsequent maintenance requirements of this study can support practitioners in the development of prospective hydrogen-powered aircraft. In particular, it allows the inclusion of maintenance implications in early design stages of corresponding system architectures. Furthermore, since the presented methodology is transferable to different design solutions, it provides a blueprint for alternative operating concepts such as the complete substitution of kerosene by hydrogen to power the main engines

Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor inverted question mark inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study

Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor- inverted question mark (TNF)-inhibitor(s). Methods:Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA ( inverted question mark4 tender, inverted question mark4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status, and Group 3 maintained dosing. During the long-term-extension (LTE), golimumab 50 mg could be increased to 100 mg, and 100 mg could be decreased to 50 mg. Data through 5 years are reported for all patients (safety) and patients using methotrexate (efficacy, intention-to-treat (ITT) analysis with last-observation-carried-forward for missing data and non-responder imputation for unsatisfactory efficacy discontinuations). Results: In total, 459 of 461 randomized patients received the study agent, 304 of whom were methotrexate-treated and included in efficacy analyses. Through week 256, the proportions of methotrexate-treated patients achieving American-College-of-Rheumatology (ACR) responses were 37.6% to 47.0% for ACR20, 21.4% to 35.0% for ACR50, and 7.8% to 17.0% for ACR70 response across randomized groups. Golimumab safety through week 268 was generally consistent with that at week 24 and week 160 and other anti-TNF agents. Conclusions:In some patients with active RA discontinuing previous TNF-antagonist therapy, golimumab safety and efficacy, assessed conservatively with ITT analyses, was confirmed through 5 years. Trial registrationClinicaltrials.gov NCT00299546. Registered 03 March 2006

Long-Term Safety and Tolerability of Apremilast Versus Placebo in Psoriatic Arthritis: A Pooled Safety Analysis of Three Phase III, Randomized, Controlled Trials.

OBJECTIVE: Psoriatic arthritis (PsA) requires long-term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3-year apremilast safety and tolerability in PsA. METHODS: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re-randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double-blind treatment continued to week 52; patients could continue apremilast during an open-label, long-term treatment phase. RESULTS: In total, 1493 patients received at least one dose of study medication and were included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) completed 3 years of treatment. Greater rates of adverse events (AEs) were reported with apremilast (61.1%; exposure-adjusted incidence rate [EAIR]/100 patient-years, 265.1) versus placebo (47.5%; EAIR/100 patient-years, 200.7) in the placebo-controlled period. During weeks 0 to ≤52, the most common AEs occurring in apremilast-exposed patients were diarrhea (13.9%; EAIR/100 patient-years, 18.6), nausea (12.3%; EAIR/100 patient-years, 16.0), headache (9.4%; EAIR/100 patient-years, 12.1), upper respiratory tract infection (9.1%; EAIR/100 patient-years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient-years, 7.7). Most AEs were mild/moderate with apremilast exposure ≤156 weeks. Rates of depression remained low (EAIR/100 patient-years, 1.8). Major adverse cardiac events (EAIR/100 patient-years, 0.5), malignancies (EAIR/100 patient-years, 0.9), and serious opportunistic infections (EAIR/100 patient-years, 0.0) were infrequent over the 3-year exposure period. Discontinuation rates due to AEs were low ( CONCLUSION: Apremilast demonstrated a favorable safety profile and was well tolerated up to 156 weeks

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies

Experimentelle Untersuchungen zur Skalierung von gepulsten laserthermischen Antrieben

Experimente in Schwerelosigkeit lassen sich auf der Erde nur mit großem Aufwand betreiben, z.B. in einem Fallturm. Als Vorstudie dafür befasst sich diesen Arbeit mit Experimenten an einem Luftkissentisch. An Pucks montierte Lightcrafts, sogenannte Flyer, schweben auf dem Luftkissen und ermöglichen Versuche in simulierter Schwerelosigkeit. Zur Durchführung der Versuche standen zwei Laser zur Verfügung: ein CO2-Hochenergielaser mit variabler Repetitionsrate und Pulsenergien bis 180 J und ein Nd:YAG-Laser mit einer Repetitionsrate von 10 Hz und max. Pulsenergie von 500 mJ. Insgesamt wurden Versuche mit vier unterschiedlichen Lightcraftgeometrien unternommen. Bei der Auswertung wurden Translation und Rotation hinsichtlich ihrer Anteile an der Gesamtenergie des Systems analysiert und mit Theoriewerten verglichen. Die Frequenzabhängigkeit der Messwerte wurde bei Mehrpulsexperimenten untersucht. Bei einigen Versuchen wurde Treibstoff verwendet. Der so gesteigerte Impulsübertrag wurde mit den Versuchen ohne Treibstoff verglichen. Dabei zeigten sich deutliche Unterschiede zwischen den einzelnen Lightcrafts. Zusätzlich wurden zum Vergleich vertikale Freiflüge durchgeführt

Flight experiments on energy scaling for in-space laser propulsion

As a preparatory study on space-borne laser propulsion, flight experiments with a parabolic thruster are carried out on an air-cushion table. The thruster is mounted like a sail on a puck allowing for laser-driven motion in three degrees of freedom (3 DOF) in artificial weightlessness. Momentum coupling is derived from point explosion theory for various parabolic thruster geometries with respect to energy scaling issues. The experimental data are compared with theoretical predictions. Vertical free flights allow for a comparison of both measurement techniques. Experimental results of air-breakdown threshold and POM ablation inside the thruster are compared with fluence data from beam propagation modeling

Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported. 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70-73% and 75-81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57-67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitorin