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Donor and Recipient Polygenic Risk Scores Influence Kidney Transplant Function
No full textKidney transplant outcomes are influenced by donor and recipient age, sex, HLA mismatch, donor type, anti-rejection medication adherence and disease recurrence, but variability in transplant outcomes remains unexplained. We hypothesise that donor and recipient polygenic burden for traits related to kidney function may also influence graft function. We assembled a cohort of 6,060 living and deceased kidney donor-recipient pairs. We calculated polygenic risk scores (PRSs) for kidney function-related traits in both donors and recipients. We investigated the association between these PRSs and recipient eGFR at 1- and 5-year post-transplant as well as graft failure. Donor: hypertension PRS (P < 0.001), eGFR PRS (P < 0.001), and intracranial aneurysm PRS (P = 0.01), along with recipient eGFR PRS (P = 0.001) were associated with eGFR at 1-year post-transplantation. Clinical factors explained 25% of the variation in eGFR at 1-year and 13% at 5-year, with PRSs cumulatively adding 1% in both cases. PRSs were not associated with long-term graft survival. We demonstrate a small, but statistically significant association between donor and recipient PRSs and recipient graft function at 1- and 5-year post-transplant. This effect is, at present, unlikely to have clinical application and further research is required to improve PRS performance.Peer reviewe
Validated Monte Carlo model of Halcyon and Ethos Radiotherapy Systems
No full textThe validated Monte Carlo (MC) model can act as a computational copy of an actual radiotherapy delivery machine and provide a reference with or without uncertainties regarding environmental variation. The reference data can be used in the validation and verification of treatment deliveries, measured data, and commercial dose calculation algorithms. The simulations provide valuable information of the dose and particle distributions inside the selected volumes. By mimicking the behavior of the actual machine, the MC model can also inherit known mechanical variations and estimate their significance as well as treatment machine design optimization.
This thesis combines the above-mentioned: the validation of the Halcyon and Ethos radiotherapy systems’ MC model, the evaluation of the treatment delivery in the clinical framework for small targets, the assessment of a mechanical uncertainty as the isocenter deviation on the systems, and the production of the reference dose distribution for the commercial dose calculation algorithms in the context of the development of a correction method to enhancing accuracy in the heterogeneous tissues of the convolution-based dose calculation.
The validation of the MC model utilizing detailed CAD-based geometry was demonstrated against both simple and complex multi-leaf collimator (MLC)-shaped fields and IAEA-compliant phase space (PHSP) files produced. The model reproduced the radiation beam characteristics, and the discrepancies between the simulation results and measurements were within acceptable limits.
After the validation, the model was used as a reference describing an ideal radiotherapy system. The delivery with a volumetric modulated arc therapy (VMAT) test plan with target sizes emulating the scale in the stereotactic treatments was assessed. Using film measurements, measured dose distributions for small targets were compared to calculations performed with Acuros External Beam (AXB) and MC simulations. The treatment delivery demonstrated high accuracy, with only minor deviations observed in steep dose gradient regions.
Based on the results and discrepancies found, the radiation isocenter deviation was identified as a mechanical uncertainty of the machine. This deviation was measured and implemented into the MC model. While the treatment system delivery met all isocenter-related specifications, the implementation of the isocenter displacement demonstrated more accurate dose predictions in comparison to the experimental data.
The validated MC model offered reference data for the study that introduced a novel method for heterogeneity correction in convolution-based dose calculations, particularly in low-density regions such as lung tissue. The simulation results supported AXB results and helped gain more confidence in the new Fourier transform dose calculation (FTDC) method with the scaling of the total energy released per mass (TERMA) according to local density and effective beam size.Tässä tutkimuksessa kehitettiin ja validoitiin laskennallinen Monte Carlo -malli Halcyon- ja Ethos-sädehoitojärjestelmille. Malli hyödyntää implementaatiossa CAD-geometriaa, mikä mahdollistaa hoitopään yksityiskohtaisen simuloinnin tarjoten tietoa annos- ja hiukkasjakaumista sekä säteilykentän ominaisuuksista. Mallin validointi toteutettiin vertaamalla simulaatiotuloksia mitattuihin arvoihin, ja tulokset osoittivat sen kykenevän toistamaan sädehoitolaitteen fysikaaliset ominaisuudet erittäin tarkasti. Näin ollen mallia voidaan pitää laskennallisena kopiona ideaalisesta sädehoitolaitteesta. Validoinnin jälkeen mallia hyödynnettiin arvioitaessa laitteiden hoitotarkkuutta pienikokoisilla hoitokohteilla sekä tutkittaessa isosentrin epäkeskisyyttä mekaanisena epävarmuustekijänä. Lisäksi malli tarjosi itsenäisen vertailukohdan kaupallisen annoslaskenta-algoritmin kehittämisen ohjaamiseksi.ei saavutettav
Plasmid-driven strategies for clone success in Escherichia coli
No full textEscherichia coli is the most widely studied microbe in history, but the population structure and evolutionary trends of its extrachromosomal elements known as plasmids remain poorly delineated. Here we used long-read technology to high-resolution sequence the entire plasmidome and the corresponding host chromosomes from an unbiased longitudinal survey covering two decades and over 2000 E. coli isolates. We find that some plasmids have persisted in lineages even for centuries, demonstrating strong plasmid-lineage associations. Our analysis provides a detailed map of recent vertical and horizontal evolutionary events involving plasmids with key antibiotic resistance, competition and virulence determinants. We present genomic evidence of both chromosomal and plasmid-driven success strategies adopted by distant lineages by independently inheriting the same genomic elements. Further, we use in vitro experiments to verify the importance of key bacteriocin-producing plasmids for clone success. Our study has general implications for understanding plasmid biology and bacterial evolutionary strategies.Peer reviewe
Jets Downstream of Collisionless Shocks : Recent Discoveries and Challenges
No full textPlasma flows with enhanced dynamic pressure, known as magnetosheath jets, are often found downstream of collisionless shocks. As they propagate through the magnetosheath, they interact with the surrounding plasma, shaping its properties, and potentially becoming geoeffective upon reaching the magnetopause. In recent years (since 2016), new research has produced vital results that have significantly enhanced our understanding on many aspects of jets. In this review, we summarise and discuss these findings. Spacecraft and ground-based observations, as well as global and local simulations, have contributed greatly to our understanding of the causes and effects of magnetosheath jets. First, we discuss recent findings on jet occurrence and formation, including in other planetary environments. New insights into jet properties and evolution are then examined using observations and simulations. Finally, we review the impact of jets upon interaction with the magnetopause and subsequent consequences for the magnetosphere-ionosphere system. We conclude with an outlook and assessment on future challenges. This includes an overview on future space missions that may prove crucial in tackling the outstanding open questions on jets in the terrestrial magnetosheath as well as other planetary and shock environments.Peer reviewe
Svenskspråkiga integrationstjänster i huvudstadsregionen : Organisationers och myndigheters roll i främjandet av ömsesidig integration
No full textMålet med denna studie har varit att fördjupa förståelsen för hur svenskspråkiga integrationstjänster fungerar i huvudstadsregionen samt att lyfta fram de möjligheter och utmaningar som olika aktörer möter i arbetet med att främja integration på svenska. Studien har strävat efter att kartlägga vilka tjänster och vilket stöd som erbjuds åt invandrare som väljer att integreras på svenska samt att undersöka hur dessa tjänster fungerar i praktiken. De centrala forskningsfrågorna har baserats på språkpolitik, en jämförelse mellan svenskspråkiga och finskspråkiga integrationstjänster, valet av integrationsspråk samt tjänsternas tillgänglighet och statistiska frågor.
Det primära forskningsmaterialet bestod av inspelade och transkriberade, semistrukturerade kvalitativa intervjuer. Intervjuerna genomfördes med sex olika aktörer som hade en tydlig koppling till det svenskspråkiga integrationsarbetet i huvudstadsregionen. Dessa aktörer var Luckan, Arbets- och näringsministeriet, Helsingfors stad, inklusive Helsingfors sysselsättningstjänster och Helsingfors Arbis, Kommunförbundet och UF-centret. Forskningsmetoden som användes var en semistrukturerad kvalitativ forskningsintervju, vilken fungerade som insamlingsmetod för materialet. Dessutom användes kvalitativ innehållsanalys som metod för databearbetning.
Resultaten samt analysen av denna studie visar att de svenskspråkiga integrationstjänsterna präglas av både utmaningar och möjligheter. Utmaningarna är kopplade till resursbrist, ojämn tillgång till tjänster samt brist på information om svenskspråkiga alternativ. Dessa utmaningar speglar i sin tur hur en jämlik språkpolitik inte alltid genomförs enligt de uppsatta målen, vilket leder till en ojämlik fördelning mellan svenskspråkiga och finskspråkiga integrationstjänster. Studien lyfter dock också fram en positiv utvecklingspotential, som bygger på ett starkare politiskt engagemang, ökade resurser och ett förbättrat samarbete mellan olika aktörer. Vidare visar analysen hur en förbättrad inkludering och effektivitet i den svenskspråkiga integrationsprocessen i huvudstadsregionen också kräver bättre insamling av statistik samt en starkare koppling mellan språkpolitikens mål och dess praktiska genomförande. Framtiden för de svenskspråkiga integrationstjänsterna beror således på ett långsiktigt och inkluderande samarbete, där alla aktörer aktivt bidrar till en genuint tvåspråkig integrationsmiljö
The perceived pedagogical competence of teacher candidates in blended learning programs in Finland
No full textThe global challenge of an insufficiency of teaching staff in Early Childhood Education (ECE) prompts initiatives such as Finland's 1000+ training project, addressing the shortage through collaboration among universities. This research concerns the initial perceptions of pedagogical understanding and competence among students embarking on a blended teacher training program aiming to integrate work and study outside university hubs. The research approach was quantitative, as we surveyed 235 adult students to shed light on the interplay between their work experience and their pedagogical competence. The data analysis involved forming sum variables and conducting one-way analyses of variance to discern statistically significant patterns in the students' responses. The results indicate significant connections between various aspects of work experience and perceived competence. Notably, the relationship between teaching experience and perceived competence in setting goals for pedagogical activities was significant. Furthermore, we identified a significant relationship between work experience and perceived competence in evaluating pedagogical activities. Hence, the study brings valuable new insights into the field of ECE teacher education in informing program development and pedagogical practices such that the existing competencies of adult students are acknowledged and further enhanced to tackle the diverse challenges of education.Peer reviewe
Alcohol use in Early Midlife : Findings from the Age 37 Follow-Up Assessment of the FinnTwin12 Cohort
No full textThis paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g., parenthood). In total, 2,085 individuals (similar to 40% of the original sample) completed the survey (551 complete twin pairs, 58.7% female, 37.3% monozygotic, M-age = 37.2 years, SD = 1.47 years, age range = 34-39 years). Individuals who participated were more likely to be female, monozygotic, and have higher parental education and less hyperactivity/impulsivity and aggression at age 12 when compared to individuals who were invited but did not participate. Parental alcohol misuse and the twins' alcohol use and misuse at age 14 were not related to study retention. Alcohol misuse in early midlife was positively associated with nicotine dependence, lifetime use of cannabis and other drugs, trauma exposure, and depressive symptoms, and negatively associated with physical health and having biological children. These new data expand upon the wealth of measures collected as part of previous assessments, expanding the scope of work on the etiology and correlates of alcohol misuse within a longitudinal, genetically-informed framework. In addition to these new survey measures, we are planning an in-person assessment to collect physiological measurements and conduct additional in-depth phenotyping on a subset of twins who have been more intensively studied over the years.Peer reviewe
Insights from a methylome-wide association study of antidepressant exposure
No full textThis study tests the association of whole-blood DNA methylation and antidepressant exposure in 16,531 individuals from Generation Scotland (GS), using self-report and prescription-derived measures. We identify 8 associations and a high concordance of results between self-report and prescription-derived measures. Sex-stratified analyses observe nominally significant increased effect estimates in females for four CpGs. There is observed enrichment for genes expressed in the Amygdala and annotated to synaptic vesicle membrane ontology. Two CpGs (cg15071067; DGUOK-AS1 and cg26277237; KANK1) show correlation between DNA methylation with the time in treatment. There is a significant overlap in the top 1% of CpGs with another independent methylome-wide association study of antidepressant exposure. Finally, a methylation profile score trained on this sample shows a significant association with antidepressant exposure in a meta-analysis of eight independent external datasets. In this large investigation of antidepressant exposure and DNA methylation, we demonstrate robust associations which warrant further investigation to inform on the design of more effective and tolerated treatments for depression.Peer reviewe
The effect of a non-steroidal anti-inflammatory drug on the locomotor activity of reindeer (Rangifer tarandus tarandus) on their natural pastures after clamp castration—a pilot study
No full textAbstract Background During seasonal round-ups, free-grazing reindeer are gathered from natural pastures. Reindeer bulls removed from breeding are clamp castrated, traditionally without analgesia, and then returned to the grazing grounds. The new Finnish Animal Welfare Act requires the use of analgesia in painful procedures. Our earlier studies have shown that a single dose of the non-steroidal anti-inflammatory drug (NSAID) meloxicam may maintain therapeutic plasma concentrations for 2–3 days in reindeer. No studies have been conducted on the effect of meloxicam on the locomotor activity of free-ranging castrated reindeer after castration. We installed GPS collars on 16 male reindeer (at least 5 years old, 130–160 kg), chosen to be castrated as a standard procedure during the round-up held on 5 Oct 2020. Of these, eight were randomly selected to receive approximately 0.5 mg/kg of meloxicam subcutaneously (NSAID group) and eight received no analgesia (TRAD group). The trackers were set to provide location twice per hour with 10 m accuracy. From the GPS data, we calculated the daily distances travelled by the reindeer during the 3 days after castration and analysed the differences between the treatments using a GEE model. Fixed factors were treatment (NSAID or TRAD), days (1–3) and hours, and the interactions between these variables. Our key presumption was that a meloxicam injection can reduce the pain related restless locomotion of newly clamp castrated reindeer. Results The overall mean ± SE daily distances travelled by NSAID (n = 8) and TRAD (n = 8) reindeer did not differ (6.60 ± 0.67 km vs. 8.60 ± 1.54 km). However, all reindeer (n = 16) moved more on day 1 than day 3. TRAD reindeer travelled farther than NSAID on day 1 (11.67 ± 2.25 km vs. 7.08 ± 0.61 km, P 0.1). NSAID movement remained stable between the days (P > 0.1), while TRAD activity declined (P = 0.002), levelling with NSAID by day 3. Daytime distances exceeded nighttime distances on days 2 and 3, with TRAD showing more disrupted daily rhythms. Conclusions Meloxicam may reduce restlessness in newly castrated reindeer, changing postoperative locomotor activity patterns in a way that suggests pain alleviation during the first 2–3 days following clamp castration. Further studies are needed on the use of analgesia and GPS collars for pain monitoring in freely grazing reindeer
Muovitiekartan mittarit
No full textTämä raportti kokoaa saatavilla olleet tiedot Suomen Muovitiekartta 2.0 -toimenpideohjelmassa esitetyistä mittareista, arvioi kehityskulkuja sekä nostaa esille tietojen puutteita ja epävarmuuksia. Raportti noudattelee Muovitiekartan rakennetta ja sanamuotoja. Tätä raporttia voidaan hyödyntää Muovitiekartan päivittämisen ja seurannan sekä mittariston kehittämisen tukena.
Mittareiden pohjaksi löytyi vain vähän seurantatietoa sekä lukuisia erillisiä selvityksiä. Seurantatietoa on saatavilla muovipakkausjätteiden kierrätysmääristä ja merenrantojen makromuoviroskasta. Tulosten mukaan muovipakkausjätteen kierrätysaste on vielä kaukana asetetusta tavoitteesta. Merenrantojen makromuoviroskan määrä on vähentynyt. Kokonaisuudessaan muovien kiertotaloussiirtymän mittaamisen tietopohja on heikko, eikä monien Muovitiekartan tavoitteiden saavuttamista voida mitata.
Saatavilla olevat seurantatiedot pohjautuvat lakisääteisiin seurantavelvoitteisiin, jolloin tietojen kokoaminen ja raportoiminen on tiettyjen toimijoiden vastuulla. Tulevaisuudessa uudet lakisääteiset velvoitteet esimerkiksi muovipakkausten sisältämästä kierrätysmateriaalista tuottanevat lisää seurantatietoa. Vapaaehtoisten sitoumusten pohjalta ei saada tällä hetkellä seurantatietoa.
Tämä raportti antaa ehdotuksia mittariston kehittämiseksi. Muovitiekartalle ehdotetut mittarit on luokiteltu toimenpidekokonaisuuksien mukaan, mutta niitä ei ole sidottu Muovitiekartan tavoitteiden eikä yksittäisten toimenpiteiden toteutumisen seurantaan. Hyvä kansallisen toimintaohjelman mittari vastaa ohjelman tavoitteita, on selkeästi määritelty, mittaa olennaista asiaa ja perustuu saatavilla oleviin tietoihin. Muovitiekartan mittaristoa on syytä selkeyttää, mittarien sanamuotoja täsmentää ja niiden lukumäärää karsia. Kaikkein tärkeimpien tavoitteiden saavuttamisen mittaamiseen on syytä harkita uuden tiedon tuottamista esimerkiksi toistuvien selvitysten avulla.Indikatorerna för Finlands färdplan för plast
Denna rapport sammanställer de tillgängliga data om de indikatorer som presenteras i Finlands färdplan för plast 2.0 åtgärdsprogram, utvärderar utvecklingstrender och belyser luckor och osäkerheter i datan. Rapporten följer strukturen och terminologin i färdplanen. Rapporten kan användas som stöd för att uppdatera och följa upp färdplanen och vidareutveckla indikatorsystemet.
Det finns endast lite övervakningsdata och flera separata studier som grund för indikatorerna. Data finns tillgänglig om återvinning av plastförpackningsavfall och makroplastskräp på havsstränderna. Enligt resultaten är återvinningsgraden för plastförpackningsavfall fortfarande långt från det uppsatta målet. Mängden makroplastskräp på havsstränderna har minskat. Sammanfattningsvis är dataunderlaget för att mäta övergången till en cirkulär ekonomi för plast svag, och uppnåendet av många av målen i plastfärdplanen är inte mätbara.
Tillgängliga övervakningsdata bygger på lagstadgade övervakningskrav, vilket innebär att insamling och rapportering av information är vissa verksamhetsutövares ansvar. I framtiden förväntas nya lagstadgade krav, så som kraven på återvunnet material i plastförpackningar, ge mer övervakningsinformation. För närvarande finns inga uppföljningsdata baserade på frivilliga åtaganden.
Denna rapport ger förslag om utveckling av indikatorsystemet. De indikatorer som föreslås för Plastfärdplanen är kategoriserade enligt åtgärdsområden, men de är inte kopplade ihop med uppföljningen av färdplanens mål eller genomförandet av specifika åtgärder. En bra indikator för ett nationellt handlingsprogram bör vara i linje med programmets mål, vara tydligt definierad, mäta något väsentligt och basera sig på tillgängliga data. Plastfärdplanens indikatorer bör tydliggöras, formuleringarna bör förtydligas och antalet indikatorer bör minskas. För att mäta uppnåendet av de viktigaste målen kan det vara nödvändigt att överväga att ta fram nya data, exempelvis genom upprepade undersökningar.Indicators for the Plastics Roadmap for Finland
This report compiles the available data on the indicators presented in the national programme Plastics Roadmap for Finland 2.0, evaluates trends, and highlights gaps and uncertainties in the data. It follows the structure and terminology of the Plastics Roadmap. The report can be used to support the updating and monitoring of the roadmap, as well as for further developing the indicator system.
Only a limited amount of monitoring data and several individual studies are available to support the monitoring. Data on the recycling of plastic packaging waste and macroplastic litter along coastlines is accessible. The results show that the recycling rate of plastic packaging waste is still significantly below the target level. However, the amount of macroplastic litter on the coast has decreased. In general, the availability of data for tracking the transition to the circular economy for plastics is weak, making it difficult to measure the progress of many of the Plastics Roadmap's objectives.
The available monitoring data is based on statutory monitoring obligations, and hence the responsibility for collection and reporting of the data is targeted to specific entities. In the future, new statutory requirements, such as those related to the recycled material content in plastic packaging, are expected to generate novel data sources for monitoring. Currently, no monitoring data is available based on voluntary agreements.
This report offers recommendations for improving the indicator system for monitoring the Plastics Roadmap. The indicators proposed for the roadmap are organised according to action areas, but they are not directly connected to monitoring the progress of the roadmap's goals or specific actions. A good indicator for a national program should be clearly defined, based on data available, and aligned with the program's objectives, as well as connected to the key themes of the programme. The indicator system of the Plastics Roadmap should be streamlined, with clearer wording for the indicators and a reduction in their number. For measuring the achievement of the most important goals, it may be necessary to consider producing new data, e.g., through regular studies