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1.
  • Alakukku, Laura, et al. (författare)
  • Maatalouden ympäristötuen vaikuttavuuden seurantatutkimus (MYTVAS 3) : loppuraportti
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Since 1995, agri-environmental support partly funded by the EU has formed the core of Finland’s agri-environmental policy. This system has had a variety of impacts on the relationship between agriculture and the environment. Today’s agri-environmental support is one of the packages included in the Rural Development Programme for Mainland Finland (2007–2013/2014), which both in itself and through the underlying EU legislation requires monitoring of the impacts of the measures implemented. The study monitoring the impact of the 2nd Finnish agri-environmental scheme (MYTVAS 3), which ran from 2008 to 2013, forms part of this monitoring. The MYTVAS 3 monitoring study was also financed by the Ministry of the Environment. The monitoring study was carried out by a consortium coordinated by MTT Agrifood Research Finland and including the Finnish Environment Institute (SYKE), the University of Helsinki, the Finnish Game and Fisheries Research Institute and the University of Turku.The purpose of the MYTVAS 3 monitoring study was to find out how agri-environmental support and its various measures have affected the state of the environment in agricultural areas, how agri-environmental support has affected the potential for farming and how agri-environmental support should be developed to increase its impact. The monitoring focused on the impacts of agri-environmental support on the nutrient load from agriculture on the waterways and on biodiversity. When evaluating the findings presented, we should remember that while monitoring data shows that something happened, it does not necessarily explain what caused it. It is not always possible to show that particular developments were a specific outcome of the current agri-environmental support system and the implementation of its measures. The delay between a measure and its observed impact is often long, and the cause-and-effect relationships are complicated and partly unknown. Also, other agricultural policy and fluctuations on the market may affect the state of the agricultural environment directly or indirectly.The monitoring data show that agri-environmental support has not had a detrimental impact on the potential for farming. Despite a slight increase in the incidence of weeds, they do not cause problems of the kind that would require amendments to the content of agri-environmental measures. Carbon levels in the surface stratum of arable land seems to be continuing their slow decline, and there is still need for measures to preserve organic material in the soil.Compliance with the fertilisation limits in the agri-environmental support system would seem to have had very little impact on crop quality. Variations in the weight and protein content per hectolitre and per 1,000 seeds were of the same order between 2006 and 2012 as they were between 1995 and 2005. Crop quantities have also not been noticeably affected by compliance with the fertilisation limits. Average crop yields remained stable between 1986 and 2013, and no clearly different crop years were observed in the 2000s. It is possible, however, that the lower fertilisation levels could have lowered crop potential in the years with advantageous weather conditions in the 2000s and that protein contents have been lower in advantageous years.The monitoring data also show that the nutrient load potential of agriculture, measured by nutrient balances, has decreased continuously for nitrogen and particularly for phosphorus. The decrease in the nutrient load potential is due above all to a decrease in the use of synthetic fertilisers. The decline in nitrogen fertilisation has bottomed out in recent years, and low protein levels measured in high crop yield years show that there is no point in further reducing nitrogen fertilisation. Optimising nitrogen fertilisation according to how advantageous the growing season is and effectively using the soluble nitrogen in cattle manure are key measures in achieving reasonable nitrogen balances and good crop quality despite fluctuations in growing season conditions. New crop variants have been found to make more efficient use of nitrogen than old ones, and thus the introduction of new variants should be promoted. Despite the decrease in the nutrient balances, there are indications that nutrient loads in runoff water from domestic animal production sites are becoming an increasing problem. Indeed, the fundamental problem with the nutrient load from agriculture is the diversification of livestock farming and crop farming, which has made it more difficult to use nutrients appropriately. Therefore attention must be paid to measures that both boost the use of nutrients in manure and reduce the levels of nutrients that end up in manure. Based on nutrient load monitoring in the catchment areas of rivers, the phosphorus load per hectare of cropland has decreased in each programme period, being about 80% of the level of the first period (1995–1999) in the third period (2007–2013). Because of the increase in the area of cropland, the nitrogen load on waterways from agriculture continued to grow during the second programme period (2000–2006) but peaked in the third (2007–2013). A similar trend was found in the nitrogen load per hectare of cropland.The most important threat to biodiversity is caused by the development of landscape structure, typically involving a decrease in the number of open or half-open areas excluded from actual cultivation. The consequence of the clearing of margins and ecological islands located in crop fields, drainage measures aimed at increasing arable land and all rationalisation of cultivated areas is the diminishing of exactly those areas that are the most important from the perspective of the biodiversity of the agricultural environment. However, the measure-specific findings in the monitoring study show that biodiversity benefits have been locally achieved where measures have been implemented on a broad enough scale (biodynamic farming, traditional biotopes, wetlands, buffer zones, green fallow / nature management areas). Particular care should therefore be taken that all cultivated land continues to have a sufficient percentage of non-cultivated areas, whether they be natural meadows, nature management areas, biodiversity strips, buffer zones, filter strips, headlands, ecological islands, etc. Including the rather popular nature management areas as a new voluntary measure under basic measures was a significant contribution to biodiversity.Regarding the rural landscape, it may be noted that by visual inspection the area of cropland has remained largely unchanged, at the level of the landscape as a whole it is far more common for the landscape to become more closed than to become more open. This trend was also observed in the visual inspection of traditional biotopes, even if the openness of the meadows monitored largely remained unchanged.The only measures that directly address the reduction of gaseous emissions in the agri-environmental support system are the longterm grass cultivation on peat fields and special aid agreements for slurry injection in cropland. While other measures have indirectly affected gaseous emissions, the impact of agri-environmental support as a whole on reducing gaseous emissions from agriculture has been negligible. In general, we may conclude that the goals, content and support levels of agri-environmental support measures must be increasingly adapted and customised by region, by type of farming and by farm, because both the state of the agricultural environment and the needs of society differ greatly between different types of rural area.
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2.
  • Antoniou, Antonis C., et al. (författare)
  • A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
  • Tidskriftsartikel (refereegranskat)abstract
    • Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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3.
  • Arason, Adalgeir, et al. (författare)
  • Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families
  • 2010
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:4, s. R50-
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.
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4.
  • Bartkova, Jirina, et al. (författare)
  • Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer : MRE11 as a candidate familial cancer-predisposing gene
  • 2008
  • Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 2:4, s. 296-316
  • Tidskriftsartikel (refereegranskat)abstract
    • The MRE11, RAD50, and NBS1 genes encode proteins of the MRE11-RAD50-NBS1 (MRN) complex critical for proper maintenance of genomic integrity and tumour suppression; however, the extent and impact of their cancer-predisposing defects, and potential clinical value remain to be determined. Here, we report that among a large series of approximately 1000 breast carcinomas, around 3%, 7% and 10% tumours showed aberrantly reduced protein expression for RAD50, MRE11 and NBS1, respectively. Such defects were more frequent among the ER/PR/ERBB2 triple-negative and higher-grade tumours, among familial (especially BRCA1/BRCA2-associated) rather than sporadic cases, and the NBS1 defects correlated with shorter patients' survival. The BRCA1-associated and ER/PR/ERBB2 triple-negative tumours also showed high incidence of constitutively active DNA damage signalling (gamma H2AX) and p53 aberrations. Sequencing the RAD50, MRE11 and NBS1 genes of 8 patients from non-BRCA1/2 breast cancer families whose tumours showed concomitant reduction/loss of all three MRN-complex proteins revealed two germline mutations in MRE11: a missense mutation R202G and a truncating mutation R633STOP (R633X). Gene transfer and protein analysis of cell culture models with mutant MRE11 implicated various destabilization patterns among the MRN complex proteins including NBS1, the abundance of which was restored by re-expression of wild-type MRE11. We propose that germline mutations qualify MRE11 as a novel candidate breast cancer susceptibility gene in a subset of non-BRCA1/2 families. Our data have implications for the concept of the DNA damage response as an intrinsic anti-cancer barrier, various components of which become inactivated during cancer progression and also represent the bulk of breast cancer susceptibility genes discovered to date.
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5.
  • Couch, Fergus J., et al. (författare)
  • Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
  • 2016
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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6.
  • de las Fuentes, Lisa, et al. (författare)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Tidskriftsartikel (refereegranskat)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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7.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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8.
  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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9.
  • Heikkinen, Milja, et al. (författare)
  • Climate partners of Helsinki : Participation-based structures and performance in a city-to-business network addressing climate change in 2011-2018
  • 2022
  • Ingår i: Urban Climate. - : Elsevier. - 2212-0955. ; 45
  • Tidskriftsartikel (refereegranskat)abstract
    • Private actors are important for urban climate action, because the public sector can control the carbon footprint of a city only partly. Public-private partnerships have been created through different voluntary approaches, such as city-level voluntary networks for companies with the aim to engage private actors in climate change mitigation and to support learning processes by bringing different actors together. If these processes are to happen, network members should connect with each other through voluntary networking activities. These connections can be studied using methods from network science. As a case example, we study the event-participationbased structures of the Climate Partners network of the City of Helsinki between 2011 and 2018, and develop an index to measure whether active event participation by a company is associated with taking more ambitious mitigation measures. The results show that the network manages to bring together companies from different fields but has difficulties with engaging them and encouraging ambitious climate goals. Our results can help to further develop networking activities. The tools we develop and share allow the replication of the analysis for other data sets, offering a basis for a comparative analysis of different networks. This opens new horizons for studying public-private networking and its effects.
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10.
  • Heikkinen, Tuomas, et al. (författare)
  • The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype
  • 2009
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 15:9, s. 3214-22
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To determine the effect of the breast cancer susceptibility mutation PALB2 1592delT on tumor phenotype and patient survival. EXPERIMENTAL DESIGN: We defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 BRCA1 and 104 BRCA2 mutation carrier cases. RESULTS: The PALB2 1592delT mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% CI), 2.65-97.78; P < 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% CI, 0.68-32.95; P = 0.1207) compared with two (0.2%) control individuals. Tumors of the PALB2 mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; P < 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (P = 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P = 0.0004 and P = 0.0490, respectively). Carrying a PALB2 mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% CI, 1.01-5.24; P = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; P = 0.0004). Carrying a BRCA2 mutation was also found to be an independent predictor of poor survival at 10-year follow-up (P = 0.04). CONCLUSIONS: The PALB2 1592delT mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a BRCA2 mutation on long-term breast cancer survival.
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