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| 10. |
- Palin, K, et al.
(författare)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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| 11. |
- Tanja, S, et al.
(författare)
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Air temperature triggers the recovery of evergreen boreal forest photosynthesis in spring
- 2003
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 9:10, s. 1410-1426
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Tidskriftsartikel (refereegranskat)abstract
- The timing of the commencement of photosynthesis (P-*) in spring is an important determinant of growing-season length and thus of the productivity of boreal forests. Although controlled experiments have shed light on environmental mechanisms triggering release from photoinhibition after winter, quantitative research for trees growing naturally in the field is scarce. In this study, we investigated the environmental cues initiating the spring recovery of boreal coniferous forest ecosystems under field conditions. We used meteorological data and above-canopy eddy covariance measurements of the net ecosystem CO2 exchange (NEE) from five field stations located in northern and southern Finland, northern and southern Sweden, and central Siberia. The within- and intersite variability for P-* was large, 30-60 days. Of the different climate variables examined, air temperature emerged as the best predictor for P-* in spring. We also found that 'soil thaw', defined as the time when near-surface soil temperature rapidly increases above 0degreesC, is not a useful criterion for P-*. In one case, photosynthesis commenced 1.5 months before soil temperatures increased significantly above 0degreesC. At most sites, we were able to determine a threshold for air-temperature-related variables, the exceeding of which was required for P-*. A 5-day running-average temperature (T-5) produced the best predictions, but a developmental-stage model (S) utilizing a modified temperature sum concept also worked well. But for both T-5 and S, the threshold values varied from site to site, perhaps reflecting genetic differences among the stands or climate-induced differences in the physiological state of trees in late winter/early spring. Only at the warmest site, in southern Sweden, could we obtain no threshold values for T-5 or S that could predict P-* reliably. This suggests that although air temperature appears to be a good predictor for P-* at high latitudes, there may be no unifying ecophysiological relationship applicable across the entire boreal zone.
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| 12. |
- Tanskanen, T., et al.
(författare)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
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Ingår i: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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- Morawska, L., et al.
(författare)
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Indoor aerosols: from personal exposure to risk assessment
- 2013
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947. ; 23:6, s. 462-487
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Forskningsöversikt (refereegranskat)abstract
- Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.
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| 27. |
- Neuvonen, E, et al.
(författare)
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Associations of Depressive Symptoms and Cognition in the FINGER Trial: A Secondary Analysis of a Randomised Clinical Trial
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60–77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient −0.006, 95% CI −0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (−0.140, p = 0.005) and memory (−0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung −0.096, 95% CI −0.163 to −0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions.
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- Pennanen, C, et al.
(författare)
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The effect of apolipoprotein polymorphism on brain in mild cognitive impairment: a voxel-based morphometric study
- 2006
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 22:1, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE Ε4 (n = 15) and those who were ApoE Ε4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the Ε4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.
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| 31. |
- Rumrich, I, et al.
(författare)
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Effects of maternal smoking on body size and proportions at birth: a register-based cohort study of 1.4 million births
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:2, s. e033465-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our work was to analyse the effect of maternal smoking on body size and body proportions of newborns when the mother had smoked only during the first trimester, in comparison with continued smoking after the first trimester. Furthermore, we have evaluated how growth restriction associated with maternal smoking contributes to changes in body proportions.DesignRegister-based cohort studySettingMaternal Exposure (MATEX) cohort identified from the Finnish Medical Birth Register.ParticipantsSingleton births without congenital anomalies and missing data (1.38 million) from 1 January 1991 to 31 December 2016.MethodsLogistic regression was used to quantify the effect of maternal smoking, stratified by the maternal smoking status.Outcome measuresBody proportions indicated by low brain-to-body ratio (defined as <10th percentile); high ponderal index and high head-to-length ratio (defined as >90th percentile); small body size for gestational age at birth (defined as weight, length or head circumference <10th percentile) and preterm birth (<37 weeks) and low birth weight (2500 g).ResultsContinued smoking after the first trimester was associated with high ponderal index (OR 1.26, 95% CI 1.23 to 1.28), low brain-to-body ratio (1.11, 1.07–1.15) and high head-to-length ratio (1.22, 1.19–1.26), corresponding with absolute risks of 22%, 10% and 19%, respectively). The effects were slightly lower when smoking had been quit during the first trimester. Similar effects were seen for the body size variables and low birth weight. Preterm birth was not associated with smoking only during first trimester.ConclusionsMaternal smoking, independent of smoking duration during pregnancy, was associated with abnormal body proportions resulting from larger reduction of length and head circumference in comparison to weight. The effects of having quit smoking during the first trimester and having continued smoking after the first trimester were similar, suggesting the importance of early pregnancy as a sensitive exposure window.
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| 32. |
- Rumrich, IK, et al.
(författare)
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Smoking during pregnancy in Finland - Trends in the MATEX cohort
- 2019
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 47:8, s. 890-898
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In Finland, smoking rates in the general population are decreasing due to increased awareness of the adverse effects and tightened tobacco legislation. However, previous studies have shown that smoking in pregnant Finnish women remained as high as in the general Finnish female population at around 15% in 2010. Our aim was to describe temporal and spatial trends in smoking behaviour, and determinants of changes in smoking behaviour between first and second pregnancy. Methods: Self-reported smoking from the Finnish Medical Birth Register covered the years 1991–2015 ( N=1,435,009). The association of maternal age and socioeconomic status with smoking rate was analysed. Spatial trends were assessed at municipality level. Results: The overall smoking rate during early pregnancy remained fairly stable at around 15% from 1991 to 2015, but increased in teenage and young women below 25 years of age. The mean smoking rate (36%) was higher in these age groups than in older pregnant women (11%). Through the study period the smoking rate remained higher in blue collar workers compared with higher socioeconomic groups. Between the first and second child, on average only 4% of women started to smoke and 41% quitted. Smoking rates developed less favourably in Eastern Finland. Conclusions: The observed increase in smoking rate during pregnancy in teenage and young women is concerning. Pregnancy is a trigger point for smoking cessation in a big fraction of pregnant women. More studies are needed to explain the opposite trends of smoking rates in Northern and Western Finland compared with Eastern Finland.
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- Smuk, Olena, et al.
(författare)
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Mechanical ana corrosion properities of P/M-HIP super duplex stainless steel after different industrial heat treatments as used for large components
- 2004
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Ingår i: Materials Science and Technology. - : Informa UK Limited. - 0267-0836 .- 1743-2847. ; 20:5, s. 641-644
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical tensile and impact toughness tests and critical pitting corrosion temperature (CPT) tests were performed on samples of Duplok 27, a P/M-HIP duplex stainless steel containing copper, after heat treatments simulating industrial heat treatments of large components. It was shown that copper alloying has positive effects on mechanical tensile properties leading to hardening and more uniform deformation. No negative effects of copper alloying on corrosion resistance properties were found. A drastic drop in impact toughness values and CPT of samples cooled at controlled cooling rates is explained by the precipitation of intermetallic secondary phases or their precursors. Lower CPT of a NG-GTAW (narrow gap gas tungsten arc welding) welded joint is explained by the lower level of alloying than that of the base material. The high temperature region of precipitation of intermetallic secondary phases is shifted towards higher temperatures than assumed for Duplok 27 P/M-HIP duplex stainless steel.
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| 34. |
- Smuk, Olena, et al.
(författare)
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Microstructures of a powder metallurgy-hot-isostatically pressed super duplex stainless steel forming in industrial heat treatments
- 2004
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Science and Business Media LLC. - 1073-5623 .- 1543-1940. ; 35A:7, s. 2103-2109
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Tidskriftsartikel (refereegranskat)abstract
- The microstructures of a powder metallurgy/hot-isostatically pressed super duplex stainless steel, designed and manufactured for massive components of paper machines, were studied after heat treatments simulating the industrial production. It was shown that copper precipitates in the ferrite phase as e phase. Morphologically, the copper precipitates are of two types-nearly spherical particles of typical size from 30 to 50 nm, and rodlike particles 30- to 35-nm wide, and up to 700-nm long. The main observations on copper precipitation in modern super duplex stainless steels are similar to those in low-alloy steels. Copper particles were shown to be the nucleation sites for the formation of secondary austenite and to pin the boundaries of sigma phase.
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- Tervo, S, et al.
(författare)
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Incidence and risk factors for mild cognitive impairment: a population-based three-year follow-up study of cognitively healthy elderly subjects
- 2004
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background: </i>Mild cognitive impairment (MCI) has attracted considerable interest as a potential predictor of Alzheimer’s disease (AD). Both the apolipoprotein E (ApoE) Ε4 allele and vascular factors have been associated with a higher risk for AD, recently they have also been linked to the risk of MCI. <i>Objectives: </i>To estimate the incidence of MCI among cognitively healthy elderly subjects during a 3-year follow-up, and to evaluate the impact of demographic and vascular factors as well as the ApoE Ε4 allele on the conversion to MCI. <i>Methods: </i>At baseline, the cognitive abilities of 806 out of 1,150 eligible subjects (aged 60–76 years) from a population-based sample were examined. Cognitively intact subjects (n = 747) were followed for an average of 3 years. <i>Results: </i>66 subjects (8.8%) had converted to MCI. The global incidence rate of MCI was 25.94/1,000 person-years. Persons with higher age (OR 1.08, 95% CI 1.01–1.16), ApoE Ε4 allele carriers (OR 2.04, 95% CI 1.15–3.64) and persons with medicated hypertension (OR 1.86, 95% CI 1.05–3.29) were more likely to convert to MCI than those individuals of lower age and without an ApoE Ε4 allele or medicated hypertension. Persons with high education (OR 0.79, 95% CI 0.70–0.89) were less likely to convert to MCI than persons with low or no education. In subjects with both the ApoE Ε4 allele and medicated hypertension, the crude OR for conversion was 3.92 (95% CI 1.81–8.49). In subjects with cardiovascular disease, the crude OR for conversion was 2.13 (95% CI 1.26–3.60). Gender, elevated blood pressure, diabetes or cerebrovascular disease had no significant effect on the conversion to MCI. <i>Conclusion:</i> Higher age, the presence of at least one ApoE Ε4 allele and medicated hypertension are independent risk factors, but high education is a protective factor for MCI. The results suggest that vascular factors may have an important role in the pathogenesis of MCI.
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- Vuorinen, Ilppo, et al.
(författare)
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Scenario simulations of future salinity and ecological consequences in the Baltic Sea and adjacent North Sea areas-implications for environmental monitoring
- 2015
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Ingår i: Ecological Indicators. - : Elsevier BV. - 1470-160X .- 1872-7034. ; 50, s. 196-205
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Tidskriftsartikel (refereegranskat)abstract
- Substantial ecological changes occurred in the 1970s in the Northern Baltic during a temporary period of low salinity (S). This period was preceded by an episodic increase in the rainfall over the Baltic Sea Watershed area. Several climate models, both global and regional, project an increase in the runoff of the Northern latitudes due to proceeding climate change. The aim of this study is to model, firstly, the effects on Baltic Sea salinity of increased runoff due to projected global change and, secondly, the effects of salinity change on the distribution of marine species. The results suggest a critical shift in the S range 5-7, which is a threshold for both freshwater and marine species distributions and diversity. We discuss several topics emphasizing future monitoring, modelling, and fisheries research. Environmental monitoring and modelling are investigated because the developing alternative ecosystems do not necessarily show the same relations to environment quality factors as the retiring ones. An important corollary is that the observed and modelled S changes considered together with species' ranges indicate what may appear under a future climate. Consequences could include a shift in distribution areas of marine benthic foundation species and some 40-50 other species, affiliated to these. This change would extend over hundreds of kilometres, in the Baltic Sea and the adjacent North Sea areas. Potential cascading effects, in coastal ecology, fish ecology and fisheries would be extensive, and point out the necessity to develop further the ecosystem approach in the environmental monitoring.
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