Põhja-Eesti Regionaalhaigla rindkerekasvajate andmekogu: rindkerekasvajate diagnostika ja ravi arengusuundumused 2015.–2019. aastal

2017. aastal diagnoositi Eestis 827 kopsu ning 7 tüümuse, südame, mediastiinumi või pleura pahaloomulist kasvajat. Kopsuvähk on sagedamini diagnoositud pahaloomuline kasvaja ning peamine kasvajaga seotud surmapõhjus. 60–65% Eestis diagnoositud kopsuvähi juhtudest ravitakse Põhja-Eesti Regionaalhaiglas (PERH). 2015. aastast alates sisestatakse kõik PERHi torakaalonkoloogia konsiiliumis käsitletud juhud rindkerekasvajate andmekogusse, et saada täpsemaid kliinilisi andmeid nii diagnostika kui ka ravi kohta. Viie aasta jooksul on toimunud olulisi uuendusi rindkerekasvajate diagnostikas ja ravis, mida on artiklis täpsemalt kirjeldatud

Warm summers and rich biotic communities during N-Hemisphere deglaciation

Detailed studies on fossil remains of plants or animals in glacial lake sediments are rare. As a result, environmental conditions right at the moment of deglaciation of the large N-Hemisphere ice-sheets remain largely unknown. Here we study three deglacial phases of the Fennoscandian Ice Sheet as a unique, repeated element in a long sediment record preserved at Sokli in northern Finland. We summarize extensive multi-proxy data (diatoms, phytoliths, chironomids, pollen, spores, non-pollen palynomorphs, macrofossils, lithology, loss-on-ignition, C/N) obtained on glacial lake sediments dated to the early Holocene (ca. 10 kyr BP), early MIS 3 (ca. 50 kyr BP) and early MIS 5a (ca. 80 kyr BP). In contrast to the common view of an unproductive ice-marginal environment, our study reconstructs rich ecosystems both in the glacial lake and along the shores with forest on recently deglaciated land. Higher than present-day summer temperatures are reconstructed based on a large variety of aquatic taxa. Rich biota developed due to the insolation-induced postglacial warming and high nutrient levels, the latter resulting from erosion of fresh bedrock and sediment, leaching of surface soils, decay of plant material under shallow water conditions, and sudden decreases in lake volume. Aquatic communities responded quickly to deglaciation and warm summers and reflect boreal conditions, in contrast to the terrestrial ecosystem which responded with some delay probably due to time required for slow soil formation processes. Birch forest is reconstructed upon deglaciation of the large LGM ice-sheet and shrub tundra following the probably faster melting smaller MIS 4 and MIS 5b ice-sheets. Our study shows that glacial lake sediments can provide valuable palaeo-environmental data, that aquatic biota and terrestrial vegetation rapidly accommodated to new environmental conditions during deglaciation, and that glacial lake ecosystems, and the carbon stored in their sediments, should be included in earth system modeling.Peer reviewe

Conditions for transformative learning for sustainable development: a theoretical review and approach

Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation

An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations

Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional screen to identify potential activating ERBB4 mutations from a randomly mutated ERBB4 expression library. Ten potentially activating ERBB4 mutations were identified and subjected to validation by functional and structural analyses. Two of the 10 ERBB4 mutants, E715K and R687K, demonstrated hyperactivity in all tested cell models and promoted cellular growth under two-dimensional and three-dimensional culture conditions. ERBB4 E715K also promoted tumor growth in in vivo Ba/F3 cell mouse allografts. Importantly, all tested ERBB4 mutants were sensitive to the pan-ERBB tyrosine kinase inhibitors afatinib, neratinib, and dacomitinib. Our data indicate that rare ERBB4 mutations are potential candidates for ERBB4-targeted therapy with pan-ERBB inhibitors.Statement of Significance:ERBB4 is a member of the ERBB family of oncogenes that is frequently mutated in different cancer types but the functional impact of its somatic mutations remains unknown. Here, we have analyzed the function of over 8,000 randomly mutated ERBB4 variants in an unbiased functional genetics screen. The data indicate the presence of rare activating ERBB4 mutations in cancer, with potential to be targeted with clinically approved pan-ERBB inhibitors.</p

An Inducible and Reversible Mouse Genetic Rescue System

Inducible and reversible regulation of gene expression is a powerful approach for uncovering gene function. We have established a general method to efficiently produce reversible and inducible gene knockout and rescue in mice. In this system, which we named iKO, the target gene can be turned on and off at will by treating the mice with doxycycline. This method combines two genetically modified mouse lines: a) a KO line with a tetracycline-dependent transactivator replacing the endogenous target gene, and b) a line with a tetracycline-inducible cDNA of the target gene inserted into a tightly regulated (TIGRE) genomic locus, which provides for low basal expression and high inducibility. Such a locus occurs infrequently in the genome and we have developed a method to easily introduce genes into the TIGRE site of mouse embryonic stem (ES) cells by recombinase-mediated insertion. Both KO and TIGRE lines have been engineered for high-throughput, large-scale and cost-effective production of iKO mice. As a proof of concept, we have created iKO mice in the apolipoprotein E (ApoE) gene, which allows for sensitive and quantitative phenotypic analyses. The results demonstrated reversible switching of ApoE transcription, plasma cholesterol levels, and atherosclerosis progression and regression. The iKO system shows stringent regulation and is a versatile genetic system that can easily incorporate other techniques and adapt to a wide range of applications

Looking east in Swedish archaeology : Envisioning eastern contacts in the Late Bronze Age and Early Iron Age

This paper explores how Late Bronze Age and Early Iron Age contacts between Sweden and the Volga-Kama region in Russia have been discussed in Swedish archaeology, focusing on bronze axes of the Mälar (or Akozino-Mälar) type and Ananino type. We argue that research by Finnish archaeologists has played a central role for introducing and inspiring discussions in Sweden on interactions with areas in Russia. Furthermore, we stress the importance of including eastern perspectives in debates on the Bronze Age and Early Iron Age in middle and northern Sweden.East and West in the North: Archaeology with and without borders in Northern FennoscandiaBronze Age Coast in the North: Eastern contacts and Bronze Age landscapes in Northern and Central Swede

Interpreting Late Bronze Age Uppland : Regional identity and interregional contacts

Throughout the 20th century, many researchers have emphasized the regional character of Uppland and the northern parts of the Mälaren valley in central Sweden during the Late Bronze Age. The region has been seen as a periphery in a Scandinavian Bronze Age perspective as well as a centre in a regional perspective. In particular, contacts and interaction between Uppland and areas to the east — Finland, the Baltic countries and Russia — have been much discussed and have played an important role in the interpretation of the period in the region.   This paper examines, from a research historical perspective, how the Late Bronze Age in the the Mälaren valley region, more specifically Uppland, has been studied from the late 19th century up to the present day, and how views on eastern contacts have affected interpretations of Bronze Age Uppland.

Inhumationsgravar under yngre bronsålder och äldsta järnålder i Uppland

This article focuses on the inhumation graves from the Late Bronze Age and the earliest part of the Iron Age that have been excavated in Uppland. The aim is to discuss the inhumation burial practice during the Late Bronze Age in this part of the Mälaren valley. It has been known for a long time that there was wide variety in the construction of graves and/or bone deposits from the Late Bronze Age in Uppland. Most of the graves are cremation graves, but archaeological excavations in Uppland and central Sweden in the 20th century and at the beginning of the 21st century found and investigated a few inhumation graves dated to the Late Bronze Age and the earliest part of the Iron Age. Even though inhumation graves in the area were known during most of the 20th century, they are often seen as something unknown, unexpected and unusual. Recent studies of burial traditions in the Mälaren valley during the Bronze Age have mainly focused on cremation graves,and especially the category of “cremation graves” which contain very few bones. In the article it is argued that the evidence of inhumation burials in Uppland needs tobe further examined in order to better understand the complex burial customs ofthe Late Bronze Age and the earliest Iron Age in central Sweden