| 1. |
- Becker, Julia, et al.
(författare)
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Dynamic ambulance relocation : a scoping review
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:12
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Forskningsöversikt (refereegranskat)abstract
- Objectives Dynamic ambulance relocation means that the operators at a dispatch centre place an ambulance in a temporary location, with the goal of optimising coverage and response times in future medical emergencies. This study aimed to scope the current research on dynamic ambulance relocation.Design A scoping review was conducted using a structured search in PubMed, Scopus and Web of Science. In total, 21 papers were included.Results Most papers described research with experimental designs involving the use of mathematical models to calculate the optimal use and temporary relocations of ambulances. The models relied on several variables, including distances, locations of hospitals, demographic-geological data, estimation of new emergencies, emergency medical services (EMSs) working hours and other data. Some studies used historic ambulance dispatching data to develop models. Only one study reported a prospective, real-time evaluation of the models and the development of technical systems. No study reported on either positive or negative patient outcomes or real-life chain effects from the dynamic relocation of ambulances.Conclusions Current knowledge on dynamic relocation of ambulances is dominated by mathematical and technical support data that have calculated optimal locations of ambulance services based on response times and not patient outcomes. Conversely, knowledge of how patient outcomes and the working environment are affected by dynamic ambulance dispatching is lacking. This review has highlighted several gaps in the scientific coverage of the topic. The primary concern is the lack of studies reporting on patient outcomes, and the limited knowledge regarding several key factors, including the optimal use of ambulances in rural areas, turnaround times, domino effects and aspects of working environment for EMS personnel. Therefore, addressing these knowledge gaps is important in future studies.
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| 2. |
- Bertmar, Sofia, et al.
(författare)
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Who's Most Targeted and Does My New Adblocker Really Help : A Profile-based Evaluation of Personalized Advertising
- 2021
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Ingår i: Proc. ACM CCS Workshop on Privacy in the Electronic Society (ACM WPES @CCS). - New York, NY, USA : ACM Digital Library. - 9781450385275
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Konferensbidrag (refereegranskat)abstract
- There is limited prior work studying how the ad personalization experienced by different users is impacted by the use of adblockers, geographic location, the user's persona, or what browser they use. To address this void, this paper presents a novel profile-based evaluation of the personalization experienced by carefully crafted user profiles. Our evaluation framework impersonates different users and captures how the personalization changes over time, how it changes when adding or removing an extension, and perhaps most importantly how the results differ depending on the profile's persona (e.g., interest, occupation, age, gender), geographic location (US East, US West, UK), what browser extension they use (none, AdBlock, AdBlock Plus, Ghostery, CatBlock), what browser they use (Chrome, Firefox), and whether they are logged in to their Google account. By comparing and contrasting observed differences we provide insights that help explain why some user groups may feel more targeted than others and why some people may feel even more targeted after having turned on their adblocker.
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| 3. |
- Ek, Weronica E, et al.
(författare)
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Causal effects of inflammatory protein biomarkers on inflammatory diseases
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:50
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Tidskriftsartikel (refereegranskat)abstract
- Many circulating proteins are associated with the presence or severity of disease. However, whether these protein biomarkers are causal for disease development is usually unknown. We investigated the causal effect of 21 well-known or exploratory protein biomarkers of inflammation on 18 inflammatory diseases using two-sample Mendelian randomization. We identified six proteins to have causal effects on any of 11 inflammatory diseases (FDR < 0.05, corresponding to P < 1.4 x 10(-3)). IL-12B protects against psoriasis and psoriatic arthropathy, LAP-TGF-beta-1 protects against osteoarthritis, TWEAK protects against asthma, VEGF-A protects against ulcerative colitis, and LT-alpha protects against both type 1 diabetes and rheumatoid arthritis. In contrast, IL-18R1 increases the risk of developing allergy, hay fever, and eczema. Most proteins showed protective effects against development of disease rather than increasing disease risk, which indicates that many disease-related biomarkers are expressed to protect from tissue damage. These proteins represent potential intervention points for disease prevention and treatment.
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| 4. |
- Frygner-Holm, Sara, et al.
(författare)
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Pretend Play as an Intervention for Children With Cancer : A Feasibility Study
- 2020
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Ingår i: Journal of Pediatric Oncology Nursing. - : Sage Publications. - 1043-4542 .- 1532-8457. ; 37:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Children with cancer suffer from symptoms and burdensome treatments that often cause distress to children and their families. Mortality is one aspect of cancer diagnosis, while another is the quality of life and well-being during and after the treatment. By supporting children's communication, self-efficacy and coping ability in the care situation, children are given the possibilities for increased independence and participation and are allowed to develop an influence over their care. The aim of this study was to develop and evaluate the feasibility and acceptability of an adult-facilitated pretend play intervention for children with cancer. Five children with ongoing treatment for cancer were invited to a play intervention that consisted of six to eight sessions of structured pretend play aimed at increasing participation, independence, and well-being. A mixed method design was used to evaluate the feasibility and acceptability of the play intervention. Measures were collected before and after interventions, and in conjunction with every play session. Results suggest that the children enjoyed the play intervention. Findings indicate small improvements regarding self-efficacy in care situations and equal or increased quality of life for participants. A main finding was that no adverse events or increased worrying was reported in conjunction with play sessions. Therefore, the intervention is regarded as safe, feasible, and acceptable as reported by participants and their primary caregivers and a possible means of increasing participation and independence in children with a cancer diagnosis.
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| 5. |
- Gisselsson Nord, David, et al.
(författare)
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Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.
- 2002
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 33:2, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
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| 6. |
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| 7. |
- Gullö, Jan-Olof, 1961-, et al.
(författare)
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Nobel Creations
- 2015
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Ingår i: <em></em>. - Aalborg : Aalborg universitet.
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Konferensbidrag (refereegranskat)
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| 8. |
- Gullö, Jan-Olof, 1961-, et al.
(författare)
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Nobel Creations : Producing infinite music for an exhibition
- 2015
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Ingår i: Dansk Musikforskning Online. - Aalborg : Danish Musicology Online - DMO. - 1904-237X. ; :Special ed., s. 63-80
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Tidskriftsartikel (refereegranskat)abstract
- In 2014 a collaborative artistic music production project gave rise to the development and use of new methods for composition and music production. With a specially de- signed software engine the music productions responded interactively to actions of the visitors at the Nobel Museum in Stockholm. The music was distributed by multi- ple loudspeakers in the museum hall, week after week without interruption through the four months the exhibition lasted. The results of the project show clear evidence, that the romantic ideal, that creativity and creative capacity primarily is individual, in- born and inherent, is not valid. Instead, by combining different art forms, using struc- tured project planning, aiming to develop creative actions, people can create artwork in collaboration, that far exceeds what they individually can achieve.
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| 9. |
- Herold, Nikolas, et al.
(författare)
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Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:2, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.
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| 10. |
- Höglund, Anna T, 1960-, et al.
(författare)
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Parent Perceptions of a Pretend Play Intervention for Their Children With Cancer
- 2023
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Ingår i: Journal of Nursing Research. - : Wolters Kluwer. - 1682-3141 .- 1948-965X. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough the rate of survival in childhood cancer today is close to 85%, a cancer diagnosis can still turn the world upside down for both children and parents. Often, children in oncology care are frustrated about their inability to control events and activities around them. Therapeutic pretend play has been suggested as a means to encourage children to express and handle emotions in a safe environment.PurposeThis study was developed to describe and explore parents' experiences of a pretend play intervention that consisted of six to eight play sessions with a play facilitator administered to their children undergoing cancer treatment.MethodsA descriptive qualitative method was used, including individual interviews with 15 parents.ResultsThree main categories were developed, including (a) experiences of joining the project, (b) perceptions of the play intervention, and (c) reflections on effects and implications, with subcategories evolved for each category. The parents experienced that the play sessions helped improve their children's communication skills and made them more capable of participating in their care. They appreciated that the intervention focused on the child's well-being and saw it as a positive break in their child's cancer treatment. It also helped them better reflect on their own situation.Conclusions/Implications for PracticeAccording to the parents' experiences, pretend play can be a helpful tool for improving children's participation in their cancer care that strengthens their autonomy, emotional repertoire, and communication skills. However, the results also highlighted that some of the children did not fully understand the information provided about this study, which weakened the validity of their consent to participate. Thus, more work is needed on developing age-appropriate information to obtain participation consent from children. In addition, more knowledge is needed regarding how to appropriately include children with cancer in research in an ethically acceptable way.
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| 11. |
- Höglund, Jonas, et al.
(författare)
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Analys av faktorer som påverkar den svenska pelletsmarknaden
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna studie är att studera vilka faktorer som påverkar efterfrågan på fasta biobränslen från Sverige med fokus på pellets samt i vilken utsträckning. Målet är att identifiera och beskriva de omvärldsfaktorer som i störst utsträckning påverkar efterfrågan på fasta svenska pellets och hur dessa faktorer samspelar med varandra. Analysen grundas på en aktörsbaserad sensitivitetsmodell där marknaden beskrivs och studeras tillsammans med en extern expertgrupp. Enligt denna studie verkar efterfrågan på pellets både från storskaliga och småskaliga kunder påverkas av flera av de andra studerade faktorerna. De fem faktorer som totalt sett bedöms påverka efterfrågan på svensk pellets mest är råvarupriset, pelletskvaliteten, temperaturvariationen jämfört med normalår, prisskillnaden mellan pellets och alternativen pga styrmedel med förutbestämd nivå samt tillgänglighet av nya råvaror. Utav dessa påverkar de fyra första efterfrågan på pellets från småskaliga kunder och de tre sista pelletsefterfrågan från storskaliga kunder.
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| 12. |
- Höglund, Jonas, et al.
(författare)
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Biofuels and land use in Sweden: an overview of land-use change effects
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Supported by policies, biofuel production has been continuously increasing worldwide during recent years. However, concerns have been raised that biofuels, often advocated as the future substitute for greenhouse gas (GHG) intensive fossil fuels, may cause negative effects on the climate and the environment. When assessing GHG emissions from biofuels, the production phase of the biofuel crop is essential since this is the phase in which most of the GHG emissions occur during the life cycle of the fuel, often linked to land use and land management. Changes in land use can result from a wide range of anthropogenic activities including agriculture and forestry management, livestock and biofuel production. The report first presents a review of the literature in the different scientific areas related to land use change (LUC) and biofuel production. Knowledge gaps related to LUC is compiled and, a synthesis is developed highlighting major challenges and key findings. Main findings are that (i) deforestation, forest management, and climate change deforestation is a major contributor to GHG emissions and can contribute to soil erosion and carbon stock changes, (ii) albedo changes and the timing of emissions need to be better understood, (iii) to avoid degradation of biodiversity great care must be taken to develop sustainable biofuel production (iv) nutrient leakage and removal of forest residues can influence the biomass growth potential (v) to avoid fertility losses in agricultural soils during biofuel production, crops with low fertilizer needs, high nutrient use efficiency and high yields should be given priority (vi) indirect effects on land use are extremely complex to quantify without great uncertainty (vii) biofuels contribution to rising food prices and poverty even more challenging (viii) biofuel production can create jobs but also interfere with traditional ways of life and recreational values, (ix) to avoid negative effects, biofuel production should be developed in collaboration with the stakeholders involved: farmers, land owners, tourists, and industry. The literature review and synthesis presented in this report shows that land use on this planet is already placing high stress on ecosystems, atmosphere, soils and human life. Because of increased biofuel production, land use change is therefore at risk of aggravating these problems. Conclusions drawn are that the LUC caused by increasing use of biofuels can be negative to various degrees but that drawbacks can be mitigated through policy measures or technology developments. Examples include the cultivation of high-yielding crops, cultivation on abandoned arable land, and effective use of by-products and waste. To explore the opportunities that exist for beneficial land use change, continued responsible and sensitive collaboration between industry, policy-makers, researchers and local communities is a prerequisite.
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| 13. |
- Höglund, Julia, et al.
(författare)
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Characterization of the human ABO genotypes and their association to common inflammatory and cardiovascular diseases in the UK Biobank
- 2021
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Ingår i: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 96:11, s. 1350-1362
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Tidskriftsartikel (refereegranskat)abstract
- The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease-related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups.
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| 14. |
- Höglund, Julia, et al.
(författare)
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Gene-based variant analysis of whole-exome sequencing in relation to eosinophil count
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils play important roles in the release of cytokine mediators in response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we have analyzed 200,000 whole-exome sequences (WES) from the UK Biobank cohort and performed gene-based analyses of eosinophil count. We defined five different variant weighting schemes to incorporate information on both deleteriousness and frequency. A total of 220 genes in 55 distinct (>10 Mb apart) genomic regions were found to be associated with eosinophil count, of which seven genes (ALOX15, CSF2RB, IL17RA, IL33, JAK2, S1PR4, and SH2B3) are driven by rare variants, independent of common variants identified in genome-wide association studies. Two additional genes, NPAT and RMI1, have not been associated with eosinophil count before and are considered novel eosinophil loci. These results increase our knowledge about the effect of rare variants on eosinophil count, which can be of great value for further identification of therapeutic targets.
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| 15. |
- Höglund, Julia, et al.
(författare)
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Improved power and precision with whole genome sequencing data in genome-wide association studies of inflammatory biomarkers
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified associations between thousands of common genetic variants and human traits. However, common variants usually explain a limited fraction of the heritability of a trait. A powerful resource for identifying trait-associated variants is whole genome sequencing (WGS) data in cohorts comprised of families or individuals from a limited geographical area. To evaluate the power of WGS compared to imputations, we performed GWAS on WGS data for 72 inflammatory biomarkers, in a kinship-structured cohort. When using WGS data, we identified 18 novel associations that were not detected when analyzing the same biomarkers with genotyped or imputed SNPs. Five of the novel top variants were low frequency variants with a minor allele frequency (MAF) of <5%. Our results suggest that, even when applying a GWAS approach, we gain power and precision using WGS data, presumably due to more accurate determination of genotypes. The lack of a comparable dataset for replication of our results is a limitation in our study. However, this further highlights that there is a need for more genetic epidemiological studies based on WGS data.
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| 16. |
- Höglund, Julia, et al.
(författare)
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Owls lack UV-sensitive cone opsin and red oil droplets, but see UV light at night : Retinal transcriptomes and ocular media transmittance
- 2019
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Ingår i: Vision Research. - : Elsevier BV. - 0042-6989 .- 1878-5646. ; 158, s. 109-119
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Tidskriftsartikel (refereegranskat)abstract
- Most diurnal birds have cone-dominated retinae and tetrachromatic colour vision based on ultra-violet/violet-sensitive UV/V cones expressing short wavelength-sensitive opsin 1 (SWS1), S cones expressing short wavelength-sensitive opsin 2 (SWS2), M cones expressing medium wavelength-sensitive opsin (RH2) and L cones expressing long wavelength-sensitive opsin (LWS). Double cones (D) express LWS but do not contribute to colour vision. Each cone is equipped with an oil droplet, transparent in UV/V cones, but pigmented by carotenoids: galloxanthin in S, zeaxanthin in M, astaxanthin in L and a mixture in D cones. Owls (Strigiformes) are crepuscular or nocturnal birds with rod-dominated retinae and optical adaptations for high sensitivity. For eight species, the absence of functional SWS1 opsin has recently been documented, functional RH2 opsin was absent in three of these. Here we confirm the absence of SWS1 transcripts for the Long-eared owl (Asio otus) and demonstrate its absence for the Short-eared owl (Asio flammeus), Tawny owl (Strix aluco) and Boreal owl (Aegolius funereus). All four species had transcripts of RH2, albeit with low expression. All four species express all enzymes needed to produce galloxanthin, but lack CYP2J19 expression required to produce astaxanthin from dietary precursors. We also present ocular media transmittance of the Eurasian eagle owl (Bubo bubo) and Short-eared owl and predict spectral sensitivities of all photoreceptors of the Tawny owl. We conclude that owls, despite lacking UV/V cones, can detect UV light. This increases the sensitivity of their rod vision allowing them, for instance, to see UV-reflecting feathers as brighter signals at night.
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| 17. |
- Höglund, Julia
(författare)
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The effect of common and rare variants on inflammatory traits and diseases
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genome wide association studies (GWAS) have identified thousands of loci associated to an immense number of traits and diseases. Most associations have been to common variants, but rare variant associations are progressively being reported. Common genetic variants often have a small effect individually but can contribute to disease risk when being several, whereas rare genetic variants often have a large effect individually. In so-called complex diseases, a number of variants together contribute to alterations in disease risk. However, to what extent common and rare variants contribute in combination or separately, still needs to be characterized for many types of diseases.In Paper I, we performed a GWAS on whole-genome sequence (WGS) data from a Swedish cohort (NSPHS, Northern Swedish Population Health Study). The same cohort have previously been genotyped, and our aim was to assess the differences and possible gains of analysing WGS data instead of genotyped data. We demonstrated that we were able to gain both power and precision in increasing the support for previous associations as well as detecting novel ones.In Paper II, we assessed the ABO blood grouping system by analysing the ABO genotypes in UK Biobank. We genetically determined the ABO genotypes of all participates and investigated whether individuals with different ABO genotypes pose different risks for cardiovascular and inflammatory disease. We were able to fine-map previous associations between the ABO blood groups and cardiovascular disease, including proteins involved in coagulation. We confirmed that non-O individuals have a higher risk of blood clots, even heterozygous carriers of A and B. These results show the potential importance of implementing ABO genotypes in the clinic.In Paper III, we used whole-exome sequence (WES) data from UK Biobank to assess the genetic contribution to changes in eosinophil count. We performed gene-based analyses with five different analysis models and found novel associations to eosinophil count. We further found associations that appears to be mainly driven by rare variants in previously known eosinophil loci. Even if WES analysis is limited to coding variation, these are promising results for further validation.In Paper IV, we built upon Paper I and performed gene-based tests in relation to more than 400 protein levels measured in NSPHS. We utilised several different models, including only coding variation, only regulatory and others and used these variant-sets in different models. By taking common GWAS variants into account, we demonstrated that novel findings could still be found. We further demonstrated that the majority of all variants in NSPHS are rare but the majority of variants carried by each individual are common.This thesis has highlighted the utilisation of different kinds of genetic data, and how it can aid in both improving, fine-mapping and increasing associations to complex diseases. This work had aided in the advancements in genetic epidemiology and medical genetics. It has explored both genotyped, WGS and WES variants, highlighting how rare and common variants can be detected and characterise in relation to inflammatory disease, both as single variants and in aggregate.
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| 18. |
- Johansson, Åsa, et al.
(författare)
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Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer
- 2022
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Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: High levels of estrogen are associated with increased risk of breast and endometrial cancer and have been suggested to also play a role in the development of ovarian cancer. Cancerogenic effects of estradiol, the most prominent form of estrogen, have been highlighted as a side effect of estrogen-only menopausal hormone therapy. However, whether high levels of endogenous estrogens, produced within the body, promote cancer development, has not been fully established.Objective: We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer.Methods: Here we performed a two-sample Mendelian randomization (MR) to estimate the effect of endogenous estradiol on the risk of developing breast, endometrial, and ovarian cancer, using the UK Biobank as well as 3 independent cancer cohorts.Results: Using 3 independent instrumental variables, we showed that higher estradiol levels significantly increase the risk for ovarian cancer (OR = 3.18 [95% CI, 1.47-6.87], P = 0.003). We also identified a nominally significant effect for ER-positive breast cancer (OR = 2.16 [95% CI, 1.09-4.26], P = 0.027). However, we could not establish a clear link to the risk of endometrial cancer (OR = 1.93 [95% CI, 0.77-4.80], P = 0.160).Conclusion: Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.
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| 19. |
- Karlsson, Torgny, et al.
(författare)
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Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease.
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:9, s. 1390-1395
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Tidskriftsartikel (refereegranskat)abstract
- Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease1-3, as well as all-cause, cardiovascular-specific and cancer-specific mortality4,5. Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk of hypertension, heart attack/angina, type 2 diabetes and hyperlipidemia, and Mendelian randomization analysis showed visceral fat to be a causal risk factor for all four diseases. In particular, a large difference in causal effect between the sexes was found for type 2 diabetes, with an odds ratio of 7.34 (95% CI = 4.48-12.0) in females and an odds ratio of 2.50 (95% CI = 1.98-3.14) in males. Our findings bolster the role of visceral adiposity as a potentially independent risk factor, in particular for type 2 diabetes in Caucasian females. Independent validation in other cohorts is necessary to determine whether the findings can translate to other ethnicities, or outside the UK.
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| 20. |
- Karlsson, Torgny, et al.
(författare)
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Time-dependent effects of oral contraceptive use on breast, ovarian and endometrial cancers
- 2021
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:4, s. 1153-1162
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Tidskriftsartikel (refereegranskat)abstract
- Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the odds ratio (OR), and instantaneous risk, as measured by the hazard ratio (HR), were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer: OR=0.72 (95% CI: 0.65-0.81) and endometrial cancer: OR=0.68 (95% CI: 0.62-0.75), an association that was stronger with longer use (P<0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age: OR=1.10 (95% CI: 1.03-1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR=1.55, 95% CI: 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited.
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| 21. |
- Kierczak, Marcin, 1981-, et al.
(författare)
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Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
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| 22. |
- Lo Faro, Valeria, et al.
(författare)
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Polygenic risk scores and risk stratification in deep vein thrombosis.
- 2023
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 228, s. 151-162
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Deep vein thrombosis (DVT) is a complex disease, where 60 % of risk is due to genetic factors, such as the Factor V Leiden (FVL) variant. DVT is either asymptomatic or manifests with unspecific symptoms and, if left untreated, DVT leads to severe complications. The impact is dramatic and currently, there is still a research gap in DVT prevention. We characterized the genetic contribution and stratified individuals based on genetic makeup to evaluate if it favorably impacts risk prediction.METHODS: In the UK Biobank (UKB), we performed gene-based association tests using exome sequencing data, as well as a genome-wide association study. We also constructed polygenic risk scores (PRS) in a subset of the cohort (Number of cases = 8231; Number of controls = 276,360) and calculated the impact on the prediction capacity of the PRS in a non-overlapping part of the cohort (Number of cases = 4342; Number of controls = 142,822). We generated additional PRSs that excluded the known causative variants.RESULTS: We discovered and replicated a novel common variant (rs11604583) near the region where are located the TRIM51 and LRRC55 genes and identified a novel rare variant (rs187725533) located near the CREB3L1 gene, associated with 2.5-fold higher risk of DVT. In one of the PRS models constructed, the top decile of risk is associated with 3.4-fold increased risk, an effect that is 2.3-fold when excluding FVL carriers. In the top PRS decile, the cumulative risk of DVT at the age of 80 years is 10 % for FVL carriers, contraposed to 5 % for non-carriers. The population attributable fractions of having a high polygenic risk on the rate of DVT was estimated to be around 20 % in our cohort.CONCLUSION: Individuals with a high polygenic risk of DVT, and not only carriers of well-studied variants such as FVL, may benefit from prevention strategies.
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| 23. |
- Rask-Andersen, Mathias, 1979-, et al.
(författare)
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Adiposity and sex-specific cancer risk.
- 2023
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Ingår i: Cancer Cell. - 1535-6108 .- 1878-3686. ; 41:6, s. 1186-1197.e4
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with several types of cancer and fat distribution, which differs dramatically between sexes, has been suggested to be an independent risk factor. However, sex-specific effects on cancer risk have rarely been studied. Here we estimate the effects of fat accumulation and distribution on cancer risk in females and males. We performed a prospective study in 442,519 UK Biobank participants, for 19 cancer types and additional histological subtypes, with a mean follow-up time of 13.4 years. Cox proportional hazard models were used to estimate the effect of 14 different adiposity phenotypes on cancer rates, and a 5% false discovery rate was considered statistically significant. Adiposity-related traits are associated with all but three cancer types, and fat accumulation is associated with a larger number of cancers compared to fat distribution. In addition, fat accumulation or distribution exhibit differential effects between sexes on colorectal, esophageal, and liver cancer.
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| 24. |
- Schmitz, Daniel, 1995-, et al.
(författare)
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Genome-Wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 106:11, s. e4471-e4486
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Tidskriftsartikel (refereegranskat)abstract
- ContextEstradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved in estradiol metabolism, but few genome-wide association studies (GWAS) have been performed to characterize the genetic contribution to variation in estrogen levels.ObjectiveIdentify genetic loci affecting estradiol levels and estimate causal effect of estradiol on bone mineral density (BMD).DesignWe performed GWAS for estradiol in males (n = 147 690) and females (n = 163 985) from UK Biobank. Estradiol was analyzed as a binary phenotype above/below detection limit (175 pmol/L). We further estimated the causal effect of estradiol on BMD using Mendelian randomization.ResultsWe identified 14 independent loci associated (P < 5 × 10−8) with estradiol levels in males, of which 1 (CYP3A7) was genome-wide and 7 nominally (P < 0.05) significant in females. In addition, 1 female-specific locus was identified. Most loci contain functionally relevant genes that have not been discussed in relation to estradiol levels in previous GWAS (eg, SRD5A2, which encodes a steroid 5-alpha reductase that is involved in processing androgens, and UGT3A1 and UGT2B7, which encode enzymes likely to be involved in estradiol elimination). The allele that tags the O blood group at the ABO locus was associated with higher estradiol levels. We identified a causal effect of high estradiol levels on increased BMD in both males (P = 1.58 × 10−11) and females (P = 7.48 × 10−6).ConclusionOur findings further support the importance of the body’s own estrogen to maintain skeletal health in males and in females.
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| 25. |
- Witt, Stefanie, et al.
(författare)
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Effects of a Pretend Play Intervention on Health-Related Quality of Life in Children With Cancer: A Swedish–German Study
- 2023
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Ingår i: Journal of Pediatric Hematology/Oncology Nursing. - : Sage Publications. - 2752-7530 .- 2752-7549. ; 40:3, s. 158-169
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer diagnosis can lead to massive physical, emotional, and social burdens on children and their families. Although children have the right to be informed and participate in their care, research shows that children's views are often not considered in care situations. Thus, it is essential to strengthen children's communication and self-efficacy (SE) to convey desires and needs. The present study explores whether a play intervention is associated with improved health-related quality of life (HrQoL) and SE for communication in care situations. We hypothesize that HrQoL and SE for communication will increase from the beginning to after the pretend play intervention.Methods: Children with cancer from Germany and Sweden were enrolled. The pretend play intervention consisted of six to 10 play sessions. A heterogenic selection of questionnaires was used to measure children's HrQoL and SE before the first pretend play session and after the last play intervention.Results: Nineteen families were included in the presented analyses, including 14 self-reports of children and 19 proxy reports of parents. We found improvements in child-reported communication, and emotional and psychosocial well-being using generic and cancer-specific HrQoL measurements. Further, children's SE in care situations improved during the play intervention. Parents also reported minor improvements in the physical dimensions in both generic and chronic‐generic HrQoL, along with improvements in independence.Discussion: Overall, the cancer-specific pretend play intervention offers young children with cancer a secure environment and can contribute to their well-being, and communication skills, during or after cancer treatment.
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| 26. |
- Zetterberg, Lars, et al.
(författare)
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Energy related emissions of non-CO2 greenhouse gases and the climate impact of forest residues - a synthesis
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report describes measures to reduce non-CO2 greenhouse gas emissions and estimates CO2 emissions from using forest residues for energy due to impacts on biogenic carbon stocks. Measures to reduce emissions of methane, nitrous oxide and fluorinated gases have been described and quantified where possible. The measures presented for methane is reduced methane leakage from landfills, leakage from transmission and distribution of natural gas and methane from incomplete combustion. Landfills are currently the second largest source of methane emissions in Sweden and the potential to reduce methane leakage is estimated to be 800 kilotonnes of carbon dioxide equivalents, or more than 60% reduction from present emissions. The potential to reduce methane leakage from natural gas pipelines have not been quantified. It is estimated that methane from incomplete combustion could be almost entirely avoided. For nitrous oxide, two different measures were studied. Nitrous oxide from fluidized beds has a reduction potential estimated to around 20 %. However, a study of the reduction potential in the EU-27 shows significantly higher reduction potential. Projections of nitrous oxide emissions from road vehicles show increased emissions to 2020 despite measures. The fluorinated gases analysed is HFC leakage from air conditioners and SF6 from switchgears and switchers. The reduction potential is considered high for HFC leakage from AC in vehicles, mainly due to the replacement of HFCs with a high GWP to HFCs with lower climate impact. For sulphur hexafluoride, emission projections show only modest reductions to 2020. Den här rapporten finns endast på engelska. Svensk sammanfattning finns i rapporten.
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