Akuutin leukemian yksilöllistetty hoito

Direct translation of cancer-specific genomic information into effective personalized therapies for acute leukemias has proven to be difficult. The aim of this study was to utilize novel tools for detailed characterization of genomic, transcriptomic, and functional aberrations in acute leukemia to gain understanding of disease pathology and guide individualized therapies. The main methods used were ex vivo drug sensitivity and resistance testing (DSRT), exome and transcriptome (RNA) sequencing, all of which were facilitated by extensive biobanking. In study I, we developed DSRT platform performed on primary leukemic cells ex vivo for identification of effective patient-specific drugs. Exome and RNA sequencing of serial samples were used for molecular characterization and to understand mechanisms of acquired resistance. Although AML samples exhibited unique DSRT profiles, responses could be clustered in five distinctive groups. Individualized treatment of refractory patients with DSRT-guided therapy resulted in meaningful clinical responses in 3/7 patients. In study II, we studied molecular drivers for relapsed T-cell acute lymphoblastic leukemia (T-ALL) and found novel STAT5B mutations. Functional studies demonstrated these mutations to enhance the transcriptional activity and to induce constitutive phosphorylation of STAT5B. The mutated blasts showed elevated BCL-XL expression and sensitivity to the pan-BCL-2 inhibitor navitoclax. Targeted sequencing revealed activating STAT5B mutations in 6/68 patients. In study III, we first evaluated ex vivo BCL-2 inhibitor sensitivity of AML cells, then we systematically assessed whether these responses correlated to specific mutations or gene expression signatures. BCL-2 inhibitor sensitivity associated with mutations in IDH1/IDH2 and WT1, as well as with aberrations in chromatin modifiers. Importantly, overexpression of a specific set of HOX genes predicted highly selective responses to BCL-2 inhibition. In study IV, we developed a national hematological biobank to allow researchers to access high-quality samples with accompanying clinical data. The samples from three collection time-points—diagnosis, potential remission, and relapse—are available. For this study, we evaluated the quality of stored samples and demonstrated that extracted DNA and RNA remain usable for demanding down-stream experiments.Uudet tutkimusmenetelmät ovat syventäneet ymmärrystä syövän syntymekanismeista, mutta valtaosaan löydetyistä mutaatiosta ei tunneta vielä kohdennettuja hoitoja. Esimerkiksi aikuisten yleisimmän leukemian, akuutin myelooisen leukemian (AML), hoito on perustunut samoihin lääkeainesiin 1970-luvulta lähtien. Väitöskirjatutkimuksen tavoitteena oli löytää yksilöllistettyjä hoitomuotoja sekä lääkevastetta ennakoivia tekijöitä akuuttiin leukemiaan sairastuneille potilaille. Menetelminä käytettiin hyväksi uuden sukupolven sekvensointimenetelmiä (eksomi- ja RNA-sekvensointi) sekä kehittämäämme suurikapasiteettista lääkeseulamenetelmää. Ensimmäisessä osatyössä osoitimme, että solusalpaajahoidolle vastaamatonta AML:aa sairastaville potilaille voidaan löytää tehoavia kohdennettuja edellä mainituin menetelmin. Lisäksi havaitsimme AML-potilaiden lääkevasteiden jakautuvan viiteen eri ryhmään. Tutkimustuloksia käytettiin seitsemän potilaan hoidossa, joista kolmella todettiin vastetta käytetylle hoidolle. Toisessa osatyössä selvitimme aiemmin kuvaamattoman STAT5B-mutaation merkitystä T-soluisessa akuutissa lymfaattisessa leukemiassa (T-ALL). Tulokset osoittivat näiden mutaatioiden johtavan STAT5B-proteiinin aktivoitumiseen ja lisäävän sen kohdegeenien kopioitumista. Etenkin ohjelmoitua solukuolemaa estävän BCL-XL:n ilmentyminen lisääntyi. Osoitimme todetun mutaation johtavan tautisolujen herkkyyteen laajakirjoiselle BCL2-estäjälle, navitoklaksille. STAT5B-mutaatioita löysimme yli kahdeksalta prosentilta T-ALL potilaista. Kolmannessa osatyössä selvitimme BCL2-estäjien vastetta ennakoivia tekijöitä AML-potilailla. Tutkimuksessa tunnistettiin useita uusia venetoklaksin herkkyyttä ennustavia tekijöitä AML:ssa. Keskeisenä löydöksenä havaittiin, että HOXA- ja HOXB-geenien ilmentyminen ennusti hoitovastetta, kun taas vähäinen HOX-ilmentyminen ennakoi resistenssiä. Lisäksi mutaatiot kromatiinia muuntelevissa geeneissä WT1, IDH1 ja IDH2 ennustivat herkkyyttä BCL2-estäjille. Viimeisessä osatyössä kuvaamme kehittämämme hematologisen biopankin, johon kerätään korkealaatuisa potilasnäytteitä ja kliinisiä tietoja hematologisen tutkimuksen edistämiseksi. Tässä väitöskirjatyössä osoitimme erilaisten uusien tutkimusmenetelmien yhdistämisen soveltuvan yksilöllisen hoidon suunnitteluun, uusien tautialaryhmien tunnistamiseen sekä hoitovastetta ennakoivien tekijöiden löytämiseen

Attitudes Towards Euthanasia among the Finnish Evangelical Lutheran Clergy

The issue of legalizing euthanasia has been a longstanding topic of discussion in Finnish society for the past few decades. The support for euthanasia has increased in Finland among the general population, as well as among physicians and nurses. This study aims to address the gap in euthanasia research by focusing on the attitudes of the clergy, a group that has not been extensively studied in relation to this topic. The study utilizes both quantitative and qualitative data to examine the factors that contribute to clergy’s attitudes towards euthanasia. The theoretical framework of this study is based on the concept of religiosity, specifically in the theory of lived religion, which allows for an investigation of the interplay between individual attitudes, cultural context, and the influence of institutional structures, such as the Church. The research data consists of 19 published newspaper articles by Church experts, an electronic survey distributed through the Clergy Union of Finland, and six interviews with Finnish Evangelical Lutheran pastors. Data were collected between 2018 and 2021. This dissertation comprises four separate publications and a summary article. The first publication examines the official statements and discourses of the experts of the Evangelical Lutheran Church of Finland regarding euthanasia. The second publication presents the quantitative results from the electronic survey of the Finnish clergy’s attitudes towards euthanasia. This publication elucidates the distribution of attitudes among the clergy and the impact of gender, religiosity, and the diocese on attitudes towards euthanasia. The third publication explores the narratives behind euthanasia attitudes, particularly the influence of family background and various life events. The fourth publication delves into the religious justification further to explain the influence of religiosity on euthanasia attitudes. This summary contributes to the understanding of the clergy’s attitudes towards euthanasia, shedding light on the factors and religious justifications that underpin these attitudes. The findings demonstrate that divergent interpretations of doctrinal views and personal life experiences explain the differences in euthanasia attitudes among the clergy. These findings suggest that these factors are also relevant to other ethical and moral topics within the Church and should be taken into account in ongoing discussions

Validity of Colorado Learning Attitudes about Science Survey for a high-achieving, Finnish population

The Colorado Learning Attitudes about Science Survey (CLASS) is an instrument which is widely used in physics education to characterize students' attitudes toward physics and learning physics and compare them with those of experts. While CLASS has been extensively validated for use in the context of higher education institutions in the United States, there has been less information about its use with European students. We have studied the structural, content, and substantive aspects of validity of CLASS by first doing a confirmatory factor analysis of N = 642 sets of student answers from the University of Helsinki, Finland. The students represented a culturally and demographically different subset of university physics students than in previous studies. The confirmatory factor analysis used a 3-factor, 15-item factor structure as a starting point and the resulting factor structure was similar to the original. Just minor modifications were needed for fit parameters to be in the acceptable range. We explored the differences by student interviews and consultation of experts. With the exception of one item, they supported the new 14-item, 3-factor structure. The results show that the interpretations made from CLASS results are mostly transferable, and CLASS remains a useful instrument for a wide variety of populations.Peer reviewe

Actinomycetes in Environmental Applications

Peer reviewe

Combining Surveys and Sensors to Explore Student Behaviour

Student belongingness is important for successful study paths, and group work forms an important part of modern university physics education. To study the group dynamics of introductory physics students at the University of Helsinki, we collected network data from seven laboratory course sections of approximately 20 students each for seven consecutive weeks. The data was collected via the SocioPatterns platform, and supplemented with students’ major subject, year of study and gender. We also collected the Mechanics Baseline Test to measure physics knowledge and the Colorado Learning Attitudes about Science Survey to measure attitudes. We developed metrics for studying the small networks of the laboratory sessions by using connections of the teaching assistant as a constant. In the network, we found both demographically homogeneous and heterogeneous groups that are stable. While some students are consistently loosely connected to their networks, we were not able to identify risk factors. Based on our results, the physics laboratory course is equally successful in building strongly connected groups regardless of student demographics in the sections or the formed small groups. SocioPatterns supplemented with surveys thus provides an opportunity to look into the dynamics of students’ social networks

Combining Surveys and Sensors to Explore Student Behaviour

Student belongingness is important for successful study paths, and group work forms an important part of modern university physics education. To study the group dynamics of introductory physics students at the University of Helsinki, we collected network data from seven laboratory course sections of approximately 20 students each for seven consecutive weeks. The data was collected via the SocioPatterns platform, and supplemented with students’ major subject, year of study and gender. We also collected the Mechanics Baseline Test to measure physics knowledge and the Colorado Learning Attitudes about Science Survey to measure attitudes. We developed metrics for studying the small networks of the laboratory sessions by using connections of the teaching assistant as a constant. In the network, we found both demographically homogeneous and heterogeneous groups that are stable. While some students are consistently loosely connected to their networks, we were not able to identify risk factors. Based on our results, the physics laboratory course is equally successful in building strongly connected groups regardless of student demographics in the sections or the formed small groups. SocioPatterns supplemented with surveys thus provides an opportunity to look into the dynamics of students’ social networks

The role of mathematics and self-efficacy in learning quantum mechanics

Peer reviewe

Comparison of sample crystallinity determination methods by X-ray diffraction for challenging cellulose I materials

Cellulose crystallinity assessment is important for optimizing the yield of cellulose products, such as bioethanol. X-ray diffraction is often used for this purpose for its perceived robustness and availability. In this work, the five most common analysis methods (the Segal peak height method and those based on peak fitting and/or amorphous standards) are critically reviewed and compared to two-dimensional Rietveld refinement. A larger () and more varied collection of samples than previous studies have presented is used. In particular, samples () with low crystallinity and small crystallite sizes are included. A good linear correlation () between the five most common methods suggests that they agree on large-scale crystallinity differences between samples. For small crystallinity differences, however, correlation was not seen for samples that were from distinct sample sets. The least-squares fitting using an amorphous standard shows the smallest crystallite size dependence and this method combined with perpendicular transmission geometry also yielded values closest to independently obtained cellulose crystallinity values. On the other hand, these values are too low according to the Rietveld refinement. All analysis methods have weaknesses that should be considered when assessing differences in sample crystallinity.Peer reviewe

Self-efficacy and conceptual knowledge in quantum mechanics during teaching reforms and the COVID-19 pandemic

Physics instruction is often unable to support students' self-efficacy. The remote teaching brought on by the COVID-19 pandemic has also affected learning. We surveyed an introductory quantum mechanics course for three years during a transition into the spin first approach, adapting the student-centered prime-time learning model and using it through the remote teaching during the pandemic. Prime-time learning includes weekly meetings where students and instructors discuss in a small group, and the assessment is based on exercises, group work, and self-assessment. We show that this teaching method improved students' self-efficacy. Students' conceptual knowledge post teaching remained high throughout the teaching reform, as measured by an abbreviated Quantum Mechanics Concept Assessment test. We also find that the prime-time model is remarkably stable during remote teaching: in contrast to many other studies, we did not see a decline in conceptual learning outcomes or self-efficacy in remote teaching during the COVID-19 pandemic.Peer reviewe