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SAFE Update February 2024
(2024)
Im Rahmen dieser publikationsbasierten Dissertation wurden drei wissenschaftliche Arbeiten veröffentlicht. Als Erstautorenschaft wurde 2022 die Arbeit “Effectiveness of High-intensity Focused Ultrasound (HIFU) Therapy of Solid and Complex Benign Thyroid Nodules - A Long-term Follow up Two-center Study.” im Journal “Experimental and Clinical Endocrinology & Diabetes” veröffentlicht. Im Folgenden wird der Inhalt dieser Arbeit dargelegt. Ein kurzer Überblick über die Ergebnisse der anderen beiden mitpublizierten Arbeiten findet sich im Kapitel „Weitere Ergebnisse der Arbeitsgruppe“.
Durch die hohe Prävalenz benigner Schilddrüsenknoten sind deren Behandlungsalternativen von großem wissenschaftlichem Interesse. Dabei bildet die nebenwirkungsarme, minimalinvasive Thermoablation mittels high-intensity focused ultrasound (HIFU) eine attraktive Alternative zu herkömmlichen Verfahren wie der Schilddrüsenchirurgie oder der Radioiodtherapie. Bei der HIFU-Echotherapie werden die Schilddrüsenknoten auf 80 - 90 Grad Celsius erhitzt, sodass eine irreversible Koagulationsnekrose entsteht. Um den Therapieprozess und die Indikationsstellung von HIFU bei benignen Schilddrüsenknoten zu optimieren, ist es notwendig, genaue Studien durchzuführen.
Ziel der vorliegenden bizentrischen Langzeitstudie war, die Effektivität von HIFU-Echotherapien bei benignen Schilddrüsenknoten zu evaluieren und erstmalig den Einfluss der Knotenmorphologie auf den Therapieerfolg zu untersuchen. Vor der Therapie und in regelmäßigen Intervallen nach der Therapie wurden die Größe und die Morphologie der Schilddrüsenknoten mittels Ultraschall dokumentiert. In der retrospektiven Studie wurden Daten von 58 Patienten ausgewertet. Dabei wurde die Gesamtpopulation in eine Gruppe mit soliden und in eine Gruppe mit komplexen Knoten eingeteilt. Die durchschnittliche prozentuale Volumenreduktion in jeder Gruppe wurde mit dem Wilcoxon-Signed-Rank Test statistisch analysiert.
Die Gesamtpopulation zeigte eine Volumenreduktion der zuvor abladierten Knoten von 38.86 % nach 3 Monaten (Spannweite: 4.03 % - 91.16 %, p < 0.0001, n = 25), 42.7 % nach 6 Monaten (Spannweite: 7.36 % - 93.2 %, p < 0.0001, n = 18), 62.21 % nach 9 Monaten (Spannweite: 12.88 % - 93.2 %, p = 0.0078, n = 8) und 61.42 % nach 12 Monaten (Spannweite: 39.39 % - 93.2 %, p > 0.05, n = 4). Die soliden Knoten hatten eine Volumenreduktion von 49.98 % nach 3 Monaten (Spannweite: 4.03 % - 91.16 %, p = 0.0001, n = 15), 46.40 % nach 6 Monaten (Spannweite: 7.36 % - 93.2 %, p = 0.001, n = 11), 65.77 % nach 9 Monaten (Spannweite: 39.39 % - 93.2 %, p = 0.0156, n = 7) und 63.88 % nach 12 Monaten (Spannweite: 39.39 % - 93.2%, p > 0.05, n = 2). Komplexe Knoten hatten eine Volumenreduktion von 35.2 % nach 3 Monaten (Spannweite: 5.85 % - 68.63 %, p = 0.002, n = 10), 36.89 % nach 6 Monaten (Spannweite: 12.23 % - 68.63 %, p = 0.0156, n = 7) und 63.64 % nach 12 Monaten (Spannweite: 52,38 % - 73.91 %, p > 0.05, n = 2).
In der vorliegenden bizentrischen Langzeitstudie wurde deutlich, dass HIFU-Echotherapie eine effektive Behandlungsoption benigner Schilddrüsenknoten ist. Erstmalig gezeigt wurde der Trend, dass solide Knoten besser auf HIFU-Echotherapie ansprechen als komplexe Knoten.
Anhand der gewonnenen Ergebnisse und der neuen Erkenntnisse zum Einfluss der Knotenmorphologie auf die HIFU-Echotherapie benigner Schilddrüsenknoten kann HIFU als Therapieoption besser bewertet werden. Eine differenziertere Indikationsstellung in Bezug auf solide und komplexe Knoten wird ermöglicht und die HIFU-Echotherapie kann gegen andere thermoablative Verfahren abgewogen werden.
We investigate the applicability of the well-known multilevel Monte Carlo (MLMC) method to the class of density-driven flow problems, in particular the problem of salinisation of coastal aquifers. As a test case, we solve the uncertain Henry saltwater intrusion problem. Unknown porosity, permeability and recharge parameters are modelled by using random fields. The classical deterministic Henry problem is non-linear and time-dependent, and can easily take several hours of computing time. Uncertain settings require the solution of multiple realisations of the deterministic problem, and the total computational cost increases drastically. Instead of computing of hundreds random realisations, typically the mean value and the variance are computed. The standard methods such as the Monte Carlo or surrogate-based methods are a good choice, but they compute all stochastic realisations on the same, often, very fine mesh. They also do not balance the stochastic and discretisation errors. These facts motivated us to apply the MLMC method. We demonstrate that by solving the Henry problem on multi-level spatial and temporal meshes, the MLMC method reduces the overall computational and storage costs. To reduce the computing cost further, parallelization is performed in both physical and stochastic spaces. To solve each deterministic scenario, we run the parallel multigrid solver ug4 in a black-box fashion.
The Åland Islands archipelago enjoys a special international status sui generis, which essentially encompasses demilitarisation, neutralisation, and autonomy. This status is guaranteed under international law by the agreements of 1921, 1940, and 1947, which are still in force. Furthermore, there are convincing reasons to assume that the Åland Islands regime has grown into European customary law. By virtue of her international (treaty) obligations, Finland cannot unilaterally change this status under the present conditions, irrespective of domestic (constitutional) decisions. While integration into NATO’s collective defence system and the EU’s Common Security and Defence Policy structures is compatible with the special status of the Åland Islands, care must be taken by Finland and her partners to ensure that the obligations arising from these developments are fulfilled in accordance with the demilitarised and neutralised status of the archipelago. This includes that the use by Finnish troops for preventive defence, beyond the exceptions laid down in the 1921 Åland Agreement, is only permitted in the case (of threat) of an immediate and clearly identifiable attack.
The autonomous character of the Åland Islands was established under a League of Nations dispute settlement and implemented, inter alia, in Finnish legislation. Its essence even grew into customary law. The arrangements of 1921, however, do not constitute a bilateral treaty between Finland and Sweden. The UN assumes that the international mechanism to protect Åland’s autonomy did not become obsolete with the demise of the League of Nations, but was only “suspended until such time as an express decision has been taken by the United Nations to put it back into force”. A corresponding proposal could be submitted, in any case, both by Finland and/or Sweden or possibly even by any other UN member state, for discussion in the Sixth Committee. However, the final decision to re-activate this special mechanism would have to be adopted by the UN General Assembly.
EU Law applies to the Åland Islands in principle; however, Finland’s Accession Treaty to the EU to which Protocol No. 2 on the Åland Islands was annexed, established a number of specific rules which are still in force today. This, most notably, results in the limited application of value added tax and excise duties in the Åland Islands. Therefore, the rules on customs procedures apply with respect to the movement of goods to and from the Åland Islands. In addition, other provisions of Union law, in particular those relating to fundamental freedoms and European state aid law, may be relevant in view of the special fiscal status of the Åland Islands. However, assessing individual cases would require further information and in-depth studies. Irrespective of the requirements set out in the said Protocol, the EU is obliged to respect the national identity of Member States pursuant to Article 4 para. 2 TEU; this obligation includes respect for the special status of the Åland Islands under both international and Finnish constitutional law.
SAFE Update April 2024
(2024)
Highlights
• High resolution profile of C. pipiens' sugar diet has been obtained using UHPLC-MS.
• Artificial feeding using ornamental plants provides similar sugar profiles as observed in field collected mosquitoes.
• Metabolomic profiling found secondary metabolites and pollutants of anthropogenic use.
Abstract: Culex pipiens (Linnaeus, 1758) mosquitoes search plant sources of sugars to cope with the energetic demand of various physiological processes. The crop as part of the digestive system is devoted to the storage of sugar-based meal obtained from various nectars sources. The profiling of sugars and metabolites in the Culex pipiens’ crop is scarce, and only few studies used Liquid Chromatography – Mass Spectrometry (LC-MS), which provides broad detection for biomonitoring environmental substances and even contaminants in the sugar diet of mosquitoes populations.
Therefore, sugar and metabolite profiling were performed on crops obtained from mosquitoes exposed to plant nectar under laboratory or natural conditions by Ultra High-Performance LC-MS (UHPLC-MS). This method allowed us a precise quantitative and qualitative identification of sugar diet and associated environmental compounds in the crop of the mosquito C. pipiens. Under laboratory condition, mosquitoes were allowed to feed on either glucose solution, commercially-available flowers or field collected flowers. In addition, we collected mosquitoes from the field to compare those crop metabolomes with metabolome patterns occurring after nectar feeding in the lab.
The sugar quantities and quality obtained from the crops of mosquitoes collected in the field were similar to those crops obtained from mosquitoes that fed on commercially-available flowers and from field collected flowers with a limit of detection of 10 μg/L for sucrose, glucose and sucrose. Next to sugar compounds, we identified 2 types of amino acids, 12 natural products, and 9 pesticides.
Next to the diversity of sugar compounds, we could confirm that secondary metabolites and environmental pollutants are typically up taken from floral nectar sources by C. pipiens. The in-depth knowledge on mosquito–plant interactions may inspire the development and further optimization of mosquito trap systems and arboviral surveillance systems.