Eturauhassyövän geneettiset syntymekanismit - tie geneettisestä epidemiologiasta geenifunktioon

Perinnölliset tekijät ovat suurin eturauhassyövän yksittäinen riskitekijä iän lisäksi. Eturauhassyövän hoidossa on edelleen monia haasteita, mitkä voivat johtaa ylidiagnostiikkaan ja -hoitoon. Siksi uusien ennusteellisten biomarkkerien tarve on suuri. Geneettisten syntymekanismien tunteminen voi auttaa paitsi riskiyksilöiden tunnistamisessa, myös seulonnassa, diagnostiikassa, potilaan ennusteen arvioinnissa, hoidon suunnittelussa sekä mahdollisten (täsmä)lääkekohteiden löytämisessä. Eturauhassyövän genetiikkaa on tutkittu jo 1990-luvulta alkaen, mutta vasta viimeaikaiset tutkimukset ovat tuoneet ymmärrystä taudin hyvin heterogeenisesta geneettisestä taustasta. Tutkimustiedon karttuessa geenitietoutta on mahdollista sisällyttää myös eturauhassyövän hoitokäytäntöihin.</p

Fertility, Family Policy and Welfare Regimes

Dieser Beitrag wurde durch die zahlreichen Übereinstimmungen zwischen der genderspezifischen Wohlfahrtsstaatsforschung und der Bevölkerungsforschung im Bezug auf die Determinanten der Fertilität angeregt. Der erste Teil dieses Beitrages befasst sich mit einer Reihe von Reproduktionstheorien vor dem Hintergrund der These des genderspezifischen Wohlfahrtsstaates. Eine zentrale Parallele zwischen diesen beiden Theorien ist die Tatsache, dass bei der Analyse von Work-Life-Choices schwerpunktmäßig eine Politik untersucht wird, die eine Vereinbarkeit von Beruf und Familie ermöglicht. Folglich nimmt man an, dass sich die informelle Betreuung nachteilig auf die Vereinbarkeit von Familie und Beruf auswirkt, ebenso wie man von homogenen Präferenzen seitens der Frauen ausgeht, also voraussetzt, dass alle Frauen Beruf und Familie miteinander verbinden wollen. Dieser Ansatz trägt jedoch der informellen Betreuung sowie der Heterogenität der Frauen nicht genügend Rechnung, weder im Hinblick auf ihre Präferenzen noch in Bezug auf ihr Verhalten. Um diese Lücken zu schließen, wird im zweiten Teil dieses Beitrages ein neuer Rahmen zur Analyse der Work-Life-Choices von Frauen ausgearbeitet. Der vorgestellte Analyserahmen legt ein besonderes Augenmerk auf die Art und Weise der Förderung oder Durchsetzung formeller sowie informeller Betreuungsformen in verschiedenen Wohlfahrtsstaaten, ebenso wie auf die Auswirkungen einer solchen Förderung auf die Entscheidungen der Frauen. Ein weiterer Schwerpunkt liegt außerdem auf der Heterogenität der Frauen, sowohl im Hinblick auf ihre Präferenzen als auch in Bezug auf ihr Verhalten. Das Hauptargument besagt, dass sich die heterogenen Präferenzen von Frauen in verschiedenen Wohlfahrtsstaatstypen auf unterschiedliche Weise zu unterschiedlichen Lebensverlaufsstrategien (in puncto Beruf und Familie) hinentwickeln, da die jeweiligen Lebensstilstrategien durch die Familienpolitik in unterschiedlichem Maß gefördert oder verhindert werden. Infolgedessen differieren die Zahlen der Frauen, die sich für eine bestimmte Strategie entscheiden, ebenso wie die Fertilitätsniveaus zwischen den Wohlfahrtsstaaten. Außerdem wird angenommen, dass sich die Haushaltsressourcen auf die Entscheidungen auswirken. Die vorgebrachte These wird anhand aktueller Daten zur Familienpolitik, zu Beschäftigungsmustern sowie zur Fertilität von Frauen in den sozialdemokratischen (Dänemark, Finnland, Norwegen, Schweden), konservativen (Österreich, Belgien, Frankreich, Deutschland, Griechenland, Italien, die Niederlande, Portugal, Spanien) sowie den liberalen Wohlfahrtsstaaten (Australien, Kanada, Irland, GB und die USA) aufgezeigt. Darüber hinaus beinhaltet dieser Beitrag eine Neuinterpretation der Ergebnisse in Bezug auf die Zusammenhänge zwischen der Familienpolitik und der Erwerbstätigkeit sowie Fertilität von Frauen vor dem Hintergrund des hierin vorgestellten Rahmens.This paper is inspired by the many similarities between gendered welfare state research and demographic research on the determinants of fertility. The first part of the paper discusses some of the theories on childbearing in the light of the gendered welfare state theory. One important similarity between these two genres is that when work-life choices are studied, the emphasis is on policies which enable women to reconcile employment and family. Support for informal care is accordingly treated as having a negative influence on work-life compatibility, and women are moreover assumed to have homogeneous preferences, i.e., they are supposed to want to combine work and family. However, such an approach does not pay sufficient attention to informal care and to heterogeneity among women, either when it comes to preferences or to behaviour. To address these gaps, in the second part of the paper a new framework to analyse women’s work-life choices is developed. The suggested framework gives considerable attention to the way in which formal as well as informal care is supported or enforced in different welfare states and the consequences such support has on women’s decision making. Moreover, heterogeneity among women is emphasised, both in preferences and when it comes to behaviour. The central argument is that women’s heterogeneous preferences transform differently to different lifestyle career strategies (with regard to employment and childbearing) in different welfare state settings, as each lifestyle strategy is encouraged or discouraged by family policy to differing degrees. Hence, the number of women who choose a particular strategy, as well as the level of fertility, varies between the welfare states. In addition, household resources are assumed to influence the choices that are being made. The argument that is put forward is illustrated with recent data on family policy, women’s employment patterns and fertility in the social-democratic (Denmark, Finland, Norway, Sweden), conservative (Austria, Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain) and liberal welfare states (Australia, Canada, Ireland, the UK, the USA). Moreover, a reinterpretation of the findings on the relationship between family policy, female employment and fertility is provided in the light of the framework outlined

A Reinvented Education in Business and Accounting using a GBL Approach for soft skills

[EN] The vulnerable, dynamic and digitalizing working environments of the 2020s obviously propose new types of `newcomer¿ skills. The character of these `soft skills¿ is inherent, whereby their learning forms a challenge for educators. Researchers around the world are on the same question: how to make the learning tools and rebuilt the classroom (virtual and face-to-face) in order to cope with this digital generation? This change needs to incorporate new Skills; these skills, called Core Skills, are changing the way to teach and to learn. Motivation is the essential key to have in mind. Creating mind-sets under a strong cognitive engagement is education for the future of professionals. Gamification, Game-Based Learning (GBL), Simulations, Virtual classrooms, digital platforms with contents and many other methods are in use all around the world to change, with motivation, the perspective of students towards their own learning path. The VUCA (volatility, uncertainty, complexity and ambiguity) world brought Higher Education Institutions the discussion of the future for an education of excellence. This article intends to present a case study as a solution to combine Simulation and GBL to promote the Core Skills that students and teachers need to achieve success on the process of teaching and learning. The solution is innovative due to the main scope: the perfect connection of humanity and empathy through the use of Simulation-GBL in higher educational institutions.Part of this work was supported by the Erasmus+ program of the European Commission under Grant 2017-1-ES01-KA203- 038589 in the frame of the project CoSki21- Core Skills for 21th-century professionals. The authors would like to thank the people who have collaborated with the research answering the questionnaires.Bastos, S.; Silva, M.; Poza-Lujan, J.; Schleutker, K. (2020). A Reinvented Education in Business and Accounting using a GBL Approach for soft skills. Academic Conferences International Limited Reading, UK. 55-66. https://doi.org/10.34190/GBL.20.047S556

Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Objectives Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by pathogenic variants in the NOTCH3 gene. In Finland, the majority of CADASIL patients carry the pathogenic founder variant c.397C>T, (p.Arg133Cys), but the spectrum of other NOTCH3 variants has not been investigated previously. The aim of the study was to investigate the spectrum and prevalence of NOTCH3 variants Finnish CADASIL patients and to examine the clinical features associated with them. Materials and Methods The spectrum of NOTCH3 variants and the clinical features associated with them were retrospectively examined in 294 Finnish CADASIL patients tested during January 1996 to October 2021 in the Medical Genetics laboratory of Department of Genomics of Turku University Hospital, where practically all samples of patients with suspected CADASIL in Finland are investigated. Results The most common NOTCH3 variants in the study cohort were c.397C>T, (p.Arg133Cys) (68%) and c.3206A>G p.(Tyr1069Cys) (18%), but other less common NOTCH3 variants were detected in as many as 14% of the patients. Eight of the detected NOTCH3 variants were novel: c.520T>A,p.(Cys174Ser), c.836A>G,p.(Gln279Arg), c.1369T>G,p.(Cys457Gly), c.1338C>G,p.(Cys446Trp), c.1564T>G,p.(Cys522Gly), c.2848T>G,p.(Cys950Gly), c.6102dup,p.(Gly2035Argfs*60), and c.2410+6C>G. Other NOTCH3 variants than p.Arg133Cys and p.Tyr1069Cys were more often associated with more severe clinical features. Conclusion This study revealed the genetic and clinical spectrum of CADASIL in the Finnish population. Sequencing of the whole NOTCH3 gene performing a gene-panel or exome sequencing is recommended when suspecting CADASIL.Peer reviewe

MiRNA profiles in lymphoblastoid cell lines of Finnish prostate cancer families

201

Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families

Background: BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease.Methods: Index individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2.Results: Altogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements.Conclusions: These results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles

Dynamic Experimental Simulation of the Demise during Re-Entry Flight

There are many limitations in ground testing in the laboratory, that prohibit fully realistic simulation of the destructive entry-flight. Some of these limitations could be overcome by technical solutions, others are determined by the physics (e.g. gravitational forces acting on the test hardware). The impact of the limitations varies and have been discussed in the community for years. One of the major limitations that could be solved technically, is the testing of satellite components in a static setup. Static testing does not reproduce the dynamic re-entry environment with its changing heat flux distribution and the inertial forces. The Department of Supersonic and Hypersonic Technologies of the German Aerospace Centre DLR constantly works on improving the test facilities, setups and instrumentation and has now developed a solution that allows dynamic demise simulation in the arc heated facility L2K. This development is complementary to the implementation realised in H2K wind tunnel for measurement of the heat flux distribution on spinning samples. We present the spinning device and wind tunnel setup and show results of the first component tests in L2