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Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
Verglichen mit Laubwaldgesellschaften sind Langzeitstudien über Waldkiefern-Bestände (Pinus sylvestris L.) in Mitteleuropa selten und die Sukzessionsdynamik von Kiefernwäldern wurden in dieser Region bisher kaum untersucht. Obwohl es sich um den am stärksten von Feuern betroffenen Waldtyp in Mitteleuropa handelt, liegen lediglich wenige Daten zu den Auswirkungen von Bränden auf die Vegetation von mitteleuropäischen Kiefernwäldern vor. Außerdem sind Kiefernwälder in besonders hohem Maße von Eutrophierung betroffen, die starke Veränderungen in der Vegetation verursachen können. In der vorliegenden Studie wurden naturnahe, waldbrandbeeinflusste Kiefernwälder (Leucobryo-Pinetum) im Nationalpark Sächsische Schweiz (Sachsen, Deutschland) untersucht. Dauerbeobachtungsflächen wurden mit bis zu vier Wiederholungen von Vegetationsaufnahmen seit 1963 untersucht. Gemäß den einzelnen Waldbrandereignissen und dem Jahr der Flächeneinrichtung wurden drei Zeitreihen analysiert. (A: 1963-2012, Feuer: 1948/1953); B: 2002-2014, Feuer: 1993; C: 2002-2014, Feuer: 2000), Hierbei wurden unerwartet geringe Veränderungen der Pflanzendiversität und des Artenspektrums der Vegetation gefunden. Nur wenige Arten wurden kurzzeitig durch Waldbrände gefördert, und lediglich einzelne Arten zeigten signifikante Veränderungen in ihren Deckungsgraden in Abhängigkeit vom Waldbrandereignis. Nitrophyten fehlten weitgehend. Offenbar liegen die lokalen Stickstoff-Depositionsraten noch deutlich unter den für einen Vegetationswandel kritischen Werten. Verglichen mit Kiefernforsten und durch traditionelle Nutzung entstandenen Kiefernwäldern stellen naturnahe Bestände des Leucobryo-Pinetum einen relativ stabilen Waldtyp dar, der nur wenig von Waldbränden beeinflusst wird und langfristig nur einer trägen Sukzession unterliegt.
The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.
Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei. Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes. Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases. However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere. It is thought that amines may enhance nucleation, but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving Outdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid–amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid–dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.