Warship wrecks and their munition cargos as a threat to the marine environment and humans: The V 1302 “JOHN MAHN” from World War II

In addition to endangering sea traffic, cable routes, and wind farms, sunken warship wrecks with dangerous cargo, fuel, or munitions on board may emerge as point sources for environmental damage. Energetic compounds such as TNT (which could leak from these munitions) are known for their toxicity, mutagenicity, and carcinogenicity. These compounds may cause potential adverse effects on marine life via contamination of the marine ecosystem, and their entry into the marine and human food chain could directly affect human health. To ascertain the impending danger of an environmental catastrophe posed by sunken warships, the North Sea Wrecks (NSW) project (funded by the Interreg North Sea Region Program) was launched in 2018. Based on historical data (derived from military archives) including the calculated amount of munitions still on board, its known location and accessibility, the German World War II ship “Vorpostenboot 1302” (former civilian name - “JOHN MAHN”) was selected as a case study to investigate the leakage and distribution of toxic explosives in the marine environment. The wreck site and surrounding areas were mapped in great detail by scientific divers and a multibeam echosounder. Water and sediment samples were taken in a cross-shaped pattern around the wreck. To assess a possible entry into the marine food chain, aged mussels were exposed at the wreck, and wild fish (pouting), a sedentary species that stays locally at the wreck, were caught. All samples were analyzed for the presence of TNT and derivatives thereof by GC–MS/MS analysis. As a result, we could provide evidence that sunken warship wrecks emerge as a point source of contamination with nitroaromatic energetic compounds leaking from corroding munitions cargo still on board. Not only did we find these explosive substances in bottom water and sediment samples around the wreck, but also in the caged mussels as well as in wild fish living at the wreck. Fortunately so far, the concentrations found in mussel meat and fish filet were only in the one-digit ng per gram range thus indicating no current concern for the human seafood consumer. However, in the future the situation mayworsen as the corrosion continues. Fromour study, it is proposed that wrecks should not only be ranked according to critical infrastructure and human activities at sea, but also to the threats they pose to the environment and the human seafood consumer

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Risk assessment of war wrecks – a comprehensive approach investigating four wrecks containing munitions in the German Bight/North Sea

Shipwrecks and dumped munition continue to be a major hazard, both in the North Sea but also on a global scale. Research within the EU Interreg project North Sea Wrecks (NSW), in cooperation with the German Aerospace Centre, Institute for the Protection of Maritime Infrastructures (DLR), is generating new insights into the status of wrecks, the potential leakage of pollutants from remaining munitions loads and the effects of contamination on exposed marine organisms in the North Sea environment. Further, historical documents are generated from archives to describe ship’s history and sinking scenario. These historical findings were compared to models and images of the visual inspections of the wrecks. Further, samples of water, sediment and organisms are being analysed for traces of explosives. Combining the results of these different fields of research allows for a better understanding of the environmental risks deriving from these wrecks. This process is shown below by focusing on the wreck of the German light cruiser SMS MAINZ, which sank in 1914. Data were compared to three additional wrecks situated also within the southern German Bight. Available data about the wrecks were preliminary assessed using a wreck risk model. Finally, wrecks were ranked according to their potential environmental risk

Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis

PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy. METHODS: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected. RESULTS: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI. CONCLUSION: A broad range of actionable alterations was targeted with available molecular therapeutics. However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-022-04049-w

Thematic assessment on Hazardous Submerged Objects in the Baltic Sea - Warfare Materials in the Baltic Sea

Contemporary society’s perception of past wars is almost exclusively driven by historic sources such as film recordings, photographs and written documents that are presented in mass media. However, the legacy of these wars is still present throughout European soil and waters, including the Baltic Sea. The marine waters of every Baltic Sea state contain warfare materials. Resulting risks may be direct and short-term. Fishermen, divers, offshore wind farm constructors and beachgoers can potentially be exposed to their remains while performing their daily work or while collecting objects in the surf. Other potential effects might be indirect and long-term such as the accumulation of carcinogenic toxic substances and their metabolites in the marine food web. Since 1974 Contracting Parties of the Helsinki Convention are seeking to address the increasing environmental challenges from human activities and that were having a severe impact on the marine environment. This includes the protection of the Baltic Sea from all sources of pollution, and thus munitions in the Baltic Sea are addressed by HELCOM since 1993. The convention commits the signatories to take measures to conserve habitats and biological diversity and for the sustainable use of marine resources. In addition, warfare materials potentially constitute a hazard and an obstacle for the utilization of the sea floor for economic purposes. The global ocean economy is predicted to double in size by 2030, as compared to 2010 (OECD 2016). In the Blue Growth Strategy laid out by the European Commission the economic potential for the extended economic usage of the oceans was recognized and focus was placed on five blue growth sectors. Two of these sectors (ocean energy and seabed mining) require the ability to safely access large areas of the sea floor (European Commission 2017). In order to exploit the economic potential of the ocean energy and seabed resources sectors, the detection and removal of warfare materials in affected areas will become increasingly important (European Parliament 2021). Recently, numerous HELCOM Contracting Parties supported increasing the knowledge concerning warfare materials in the Baltic Sea and their effects on humans and the marine environment of the Baltic Sea. As a result of national, regional and international scientific research the understanding of the issue grows and consequentially numerous recommendations are published on how the warfare materials challenge can be addressed. However, international coordination is necessary to identify synergies and to avoid a duplication of efforts. This report provides the current state of knowledge on warfare materials in the Baltic sea based on recent research projects

North Sea Wrecks - An interdisciplinary approach towards understanding the risks posed by wrecks containing munitions in the North Sea

Shipwrecks and dumped munitions continue to be a major hazard in the North Sea. Research within the EU Interreg project North Sea Wrecks (NSW), in cooperation with DLR, is generating new insights into the status of wrecks, the potential leakage of pollutants from munitions loads and the effects of contamination on exposed marine organisms in the North Sea environment. Further, historical documents are compared to models and visual inspections of the wreck. Samples of water, sediment and organisms are being analysed. Combining the results of these different fields of research allows for a better understanding of the environmental risks deriving from these wrecks. The extended article will detail the wreck of the SMS Mainz as a case study

Local glucose metabolism is unaltered in reversible splenial lesion syndrome

Background and purpose: Transient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES. Methods: We retrospectively analysed patients with RESLES after reductions in antiseizure medications during in-hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests. Results: Local glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p = 0.902 and p = 0.535, respectively). Conclusion: We found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible

Kampfmittel im Meer – Der Umgang mit Belastungsschwerpunkten

Kampfmittel im Meer stellen aufgrund des von ihnen ausgehenden Risikos für die Bevölkerung und die bereits eintretende Belastung der Umwelt eine enorme Herausforderung dar. Von besonderer Bedeutung sind hierbei Belastungsschwerpunkte wie das Versenkungsgebiet Kolberger Heide. Dieser Beitrag beschreibt mögliche Maßnahmen, um mit solchen Belastungsschwerpunkten umzugehen. Hierzu gehören die Einrichtung von Sperrgebieten, die Etablierung eines Monitoring-Programms, die Durchführung historischer Recherchen sowie technischer Erkundungsarbeiten, die Räumung von Kampfmitteln und an die Öffentlichkeit gerichtete Informationskampagnen. Anschließend wird untersucht, wie diese Maßnahmen bislang in der Kolberger Heide Anwendung finden. Zuletzt werden mögliche zukünftige Maßnahmen vorgeschlagen