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J.R.R. Tolkien's "enigmatic and unfinished" book "The Silmarillion" - posthumously published by Christopher Tolkien in 1977 - is often referred to as being a mythic work, or a collection of mythopoeic tales, but what exactly does that description entail? Logically, Tolkien's writings, by virtue of being labeled 'mythic' alongside of mythologies such as "The Iliad", "Metamorphoses", and "The Odyssey", must possess qualities which warrant the description. While Tolkien's mythology is in a different category since his mythology is specifically designed for Middle-earth, there are still important overlaps through which inspiration and influences may be traced.
BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, many retrospective single-centre or specialised centre reports have shown promising mortality rates with the use of extracorporeal membrane oxygenation (ECMO) therapy. However, the mortality rate of an entire country throughout the COVID-19 pandemic remains unknown.
OBJECTIVES: The primary objective is to determine the hospital mortality in COVID-19 patients receiving venovenous ECMO (VV-ECMO) and veno-arterial ECMO (VA-ECMO) therapy. Secondary objectives are the chronological development of mortality during the pandemic, the analysis of comorbidities, age and complications.
DESIGN: Cohort study.
SETTING: Inpatient data from January 2020 to September 2021 of all hospitals in Germany were analysed.
PARTICIPANTS: All COVID-19-positive patients who received ECMO therapy were analysed according to the appropriate international statistical classification of diseases and related health problem codes (ICDs) and process key codes (OPSs).
MAIN OUTCOME MEASURES: The primary outcome was the hospital mortality.
RESULTS: In total, 4279 COVID-19-positive patients who received ECMO therapy were analysed. Among 404 patients treated with VA-ECMO and 3875 treated with VV-ECMO, the hospital mortality was high: 72% (n = 291) for VA-ECMO and 65.9% (n = 2552) for VV-ECMO. A total of 43.2% (n = 1848) of all patients were older than 60 years with a hospital mortality rate of 72.7% (n = 172) for VA-ECMO and 77.6% (n = 1301) for VV-ECMO. CPR was performed in 44.1% (n = 178) of patients with VA-ECMO and 16.4% (n = 637) of patients with VV-ECMO. The mortality rates widely varied from 48.1 to 84.4% in individual months and worsened from March 2020 (59.2%) to September 2021 (78.4%).
CONCLUSION: In Germany, a large proportion of elderly patients with COVID-19 were treated with ECMO, with an unacceptably high hospital mortality. Considering these data, the unconditional use of ECMO therapy in COVID-19 must be carefully considered and advanced age should be considered as a relative contraindication.
Background: Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. We hypothesized that mortality in Germany in ECLS therapy did not differ from previously reported literature
Methods: Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The international statistical classification of diseases and related health problems codes (ICD) and process keys (OPS) for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used.
Results: In total, 45,647 hospitalized patients treated with ECLS were analysed. In Germany, 231 hospitals provided ECLS therapy, with a median of 4 VV-ECMO and 9 VA-ECMO in 2018. Overall hospital mortality remained higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% from 825 in 2007 to 2768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. In 2018, the hospital mortality decreased in VV-ECMO patients and VV-ECMO patients with ARDS to 53.9% (n = 1493) and 54.4% (n = 926), respectively.
Conclusions: ARDS is a severe disease with a high mortality rate despite ECLS therapy. Although endpoints and timing of the evaluations differed from those of the CESAR and EOLIA studies and the Extracorporeal Life Support Organization (ELSO) Registry, the reported mortality in these studies was lower than in the present analysis. Further prospective analyses are necessary to evaluate outcomes in ECMO therapy at the centre volume level.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop- and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
In order to achieve climate change mitigation, long-term decisions are required that must be reconciled with other societal goals that draw on the same resources. For example, ensuring food security for a growing population may require an expansion of crop land, thereby reducing natural carbon sinks or the area available for bio-energy production. Here, we show that current impact-model uncertainties pose an important challenge to long-term mitigation planning and propose a new risk-assessment and decision framework that accounts for competing interests.
Based on cross-sectorally consistent simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) we discuss potential gains and limitations of additional irrigation and trade-offs of the expansion of agricultural land as two possible response measures to climate change and growing food demand. We describe an illustrative example in which the combination of both measures may close the supply demand gap while leading to a loss of approximately half of all natural carbon sinks.
We highlight current limitations of available simulations and additional steps required for a comprehensive risk assessment.
Both, gas and particle scavenging contribute to the transport of organic compounds by ice crystals in the troposphere. To simulate these processes an experimental setup was developed to form airborne ice crystals under atmospheric conditions. Experiments were performed in a wall independent reactor (WIR) installed in a walk-in cold chamber maintained constantly at -20°C. Aerosol particles were added to the carrier gas of ambient air by an aerosol generator to allow heterogeneous ice formation. Temperature variations and hydrodynamic conditions of the WIR were investigated to determine the conditions for ice crystal formation and crystal growth by vapour deposition. In detail, the dependence of temperature variations from flow rate and temperature of the physical wall as well as temperature variations with an increasing reactor depth were studied. The conditions to provide a stable aerosol concentration in the carrier gas flow were also studied. The temperature distribution inside the reactor was strongly dependent on flow rate and physical wall temperature. At an inlet temperature of -20°C, a flow rate of 30 L•min exp -1 and a physical wall temperature of +5°C turned out to provide ideal conditions for ice formation. At these conditions a sharp and stable laminar down draft "jet stream" of cold air in the centre of the reactor was produced. Temperatures measured at the chamber outlet were kept well below the freezing point in the whole reactor depth of 1.0 m. Thus, melting did not affect ice formation and crystal growth. The maximum residence time for airborne ice crystals was calculated to at 40 s. Ice crystal growth rates increased also with increasing reactor depth. The maximum ice crystal growth rate was calculated at 2.82 mg• exp -1. Further, the removal efficiency of the cleaning device for aerosol particles was 99.8% after 10 min. A reliable particle supply was attained after a preliminary lead time of 15 min. Thus, the minimum lead time was determined at 25 min. Several test runs revealed that the WIR is suitable to perform experiments with airborne ice crystals.
Preliminary data on phi production in central Pb + Pb collisions at 158 GeV per nucleon are presented, measured by the NA49 experiment in the hadronic decay channel phi - K+K-. At mid-rapidity, the kaons were separated from pions and protons by combining dE/dx and time-of-flight information; in the forward rapidity range only dE/dx identification was used to obtain the rapidity distribution and a rapidity-integrated mt-spectrum. The mid-rapidity yield obtained was dN/dy = 1.85 ± 0.3 per event; the total phi multiplicity was estimated to be 5.0 ± 0.7 per event. Comparison with published pp data shows a slight, but not very significant strangeness enhancement.
New results from the energy scan programme of NA49, in particular kaon production at 30 AGeV and phi production at 40 and 80 AGeV are presented. The K+/pi+ ratio shows a pronounced maximum at 30 AGeV; the kaon slope parameters are constant at SPS energies. Both findings support the scenario of a phase transition at about 30 AGeV beam energy. The phi/pi ratio increases smoothly with beam energy, showing an energy dependence similar to K-/pi-. The measured particle yields can be reproduced by a hadron gas model, with chemical freeze-out parameters on a smooth curve in the T-muB plane. The transverse spectra can be understood as resulting from a rapidly expanding, locally equilibrated source. No evidence for an earlier kinetic decoupling of heavy hyperons is found.
Guerillas win as long as they do not lose, and government forces lose as long as they do not win. In Afghanistan, this adage holds, once again, true. Western civilian and military leaders want us to believe that insurgents and criminals are running out of options. Indeed, after much initial stuttering, NATO has transformed into a veritable counter-insurgency machine, with the United States shouldering most of the burden. Casualties among the Taliban and other enemies of NATO are enormous. Enormous, too, is the coalition of NATO and Afghan troops, approaching half a million soldiers and militia-types.
Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. Methods A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Results Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. Conclusion There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.