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1.	Lindqvist, P. G., et al. (författare) Avoidance of sun exposure as a risk factor for major causes of death : A competing risk analysis of the Melanoma in Southern Sweden cohort 2016 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 375-387 Tidskriftsartikel (refereegranskat)abstract Objective: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. Methods: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. Results: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. Conclusion: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.
2.	Moll, Ulrika, et al. (författare) Impact of pregestational weight and weight gain during pregnancy on long-term risk for diseases 2017 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this study was to analyse the impact of maternal BMI at start of pregnancy and maternal weight gain during pregnancy on the risk of various diseases later in life. Methods: In a population-based cohort from southern Sweden, women with at least one delivery registered in the Swedish Medical Birth Register ten or more years before answering a health questionnaire were identified (n = 13,608). Complete data were found in 3,539 women. Results: Women with BMI >25 at start of pregnancy had increased risk of developing obesity (OR 21.9), diabetes (OR 6.4), cardiac disease (OR 2.7), endocrine diseases (OR 2.3), and other morbidity (OR 1.4), compared with women of normal weight. A high weight gain (>15 kg) during pregnancy was associated to later risk of overweight (OR 2.0) and obesity (OR 2.2), but not diabetes, cardiac disease, or endocrine diseases. A positive association was found between low weight gain and the risk of developing psychiatric disorders (OR 1.6). Conclusions: A high BMI at start of pregnancy significantly increased the risk of several diseases later in life. However, a high weight gain during pregnancy was only significant for future overweight and obesity. These findings have implications for both pregestational intervention and post gestational follow up of obese and overweight women.
3.	Wendin, Karin, et al. (författare) Mer krävs för att undvika svält bland äldre 2015 Ingår i: Svenska Dagbladet. - 1101-2412. ; :23 december Tidskriftsartikel (populärvet., debatt m.m.)
4.	Wendin, Karin, et al. (författare) Mer krävs för att undvika svält bland äldre 2015 Ingår i: Svenska Dagbladet. - 1101-2412. ; :23 december Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Abarkan, Abdellah, et al. (författare) Lyssna på forskningen : Den visar på avregleringens problem 2019 Ingår i: Dagens nyheter. - Stockholm : Dagens nyheter. - 1101-2447. ; :10/21/2019 Tidskriftsartikel (populärvet., debatt m.m.)
6.	Abboud, Amina, et al. (författare) Årsbok 2018 : Socialhögskolan, Lunds universitet 2019 Rapport (övrigt vetenskapligt/konstnärligt)abstract Socialhögskolans årsbok ger en liten inblick i vad vi gör och vi hoppas att den bidrar till att presentera utsnitt från vår verksamhet på ett trevligt och samlat sätt. Årsboken som är Socialhögskolans tredje uppmärksammar inte bara det som skett på Socialhögskolan under 2018. Den uppmärksammar även att 2018 var året då svensk äldreomsorg fyllde 100 år. Årsbokens gästredaktör Per Gunnar Edebalk inleder därför bokens forskningsavsnitt med att i år skriva om just hundraåringens historia. Det är inledningen på ett avsnitt där flera forskare vid Socialhögskolan bjuder på bidrag som lyfter fram aspekter av äldreomsorg och åldrande.Håkan Jönson och Tove Harnett resonerar om de begrepp som omgärdar äldreomsorgens möten och organisering sett i ett socialt arbetets perspektiv. De två har även skrivit en artikel om huruvida behov ska ses annorlunda mellan grupper bara för att man passerat en viss ålder.Däremellan presenteras en text av Erika Werner som låter oss möta frågor kring en sviken generation, här genom ett möte med Agnes, som hamnade mitt i skarven när pensionssystemet reformerades. Elisabeth Carlstedt presenterar en text om hur äldreomsorgens särskilda boenden arbetar i relation till Socialtjänstlagens direktiv om meningsfullhet och värdighet, och hur svårt det är. Lars Harrysson presenterar därefter ett avsnitt om två forskningsprojekt som han och Erika Werner gjort där fokus har legat dels på pensioner för personer i ekonomiskt utsatta grupper, speciellt med migrantbakgrund, dels om hur tro och äldreomsorg samspelar, eller inte. Äldreomsorgsavsnittet avslutas sedan med en intervju som Patrik Hekkala gjort med Peter Andersson som startade kursen socialt arbete med äldre och med Tove Harnett som tagit över och fortsatt utvecklingsarbetet till dags datum.Årsboken avslutas sedan med fyra texter. En av Amina Abboud, snart färdig socionom, som skriver om sina erfarenheter av och i uppsatsskrivandet. Sedan en där vi får möta Carina Olsson som arbetat hos oss länge, men som faktiskt arbetat vid universitetet i 40 år 2018. Emelie Dahlström, Joakim Grina och Jan Abrahamsson ger sedan en bakgrundsteckning till en hos Socialhögskolan verksam social accelerator, SoPact. Som avrundning finner du sedan lite mer information om vår verksamhet här vid Socialhögskolan.
7.	Abdalmoaty, Mohamed, 1986- (författare) Learning Stochastic Nonlinear Dynamical Systems Using Non-stationary Linear Predictors 2017 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract The estimation problem of stochastic nonlinear parametric models is recognized to be very challenging due to the intractability of the likelihood function. Recently, several methods have been developed to approximate the maximum likelihood estimator and the optimal mean-square error predictor using Monte Carlo methods. Albeit asymptotically optimal, these methods come with several computational challenges and fundamental limitations.The contributions of this thesis can be divided into two main parts. In the first part, approximate solutions to the maximum likelihood problem are explored. Both analytical and numerical approaches, based on the expectation-maximization algorithm and the quasi-Newton algorithm, are considered. While analytic approximations are difficult to analyze, asymptotic guarantees can be established for methods based on Monte Carlo approximations. Yet, Monte Carlo methods come with their own computational difficulties; sampling in high-dimensional spaces requires an efficient proposal distribution to reduce the number of required samples to a reasonable value.In the second part, relatively simple prediction error method estimators are proposed. They are based on non-stationary one-step ahead predictors which are linear in the observed outputs, but are nonlinear in the (assumed known) input. These predictors rely only on the first two moments of the model and the computation of the likelihood function is not required. Consequently, the resulting estimators are defined via analytically tractable objective functions in several relevant cases. It is shown that, under mild assumptions, the estimators are consistent and asymptotically normal. In cases where the first two moments are analytically intractable due to the complexity of the model, it is possible to resort to vanilla Monte Carlo approximations. Several numerical examples demonstrate a good performance of the suggested estimators in several cases that are usually considered challenging.
8.	Adawi, Tom, 1970, et al. (författare) Characterizing Software Engineering Students' Discussions during Peer Instruction : Opportunities for Learning and Implications for Teaching 2016 Ingår i: International Journal of Engineering Education. - 0949-149X. ; 32:2, s. 927-936 Tidskriftsartikel (refereegranskat)abstract Peer instruction is a method for activating students during lectures, which has gained a considerable amount of attention in higher education due to claims of dramatic improvement in learning gains. The purpose of this qualitative research study is to investigate what types of discussions engineering students engage in during a peer instruction session and what learning possibilities that are enabled by these different types of discussions. We observed twelve students during six separate and simulated peer instruction sessions and the students were interviewed individually after the sessions.Ananalysis of the data revealed that the students engaged in three qualitatively different types of discussions: affirmative discussions, motivating discussions, and argumentative discussions. We characterize these different types of discussions in terms of the number of alternative answers the students discuss, the extent to which they draw on prior knowledge and experiences, as well as the fundamental difference between an explanation and an argument. A good opportunity for learning is opened up when students are aspiring to find the truth, not simply being satisfied with what they believe to be true. We conclude that students do not always engage in discussions that support their learning in the best way, and we discuss implications for using peer instruction as a teaching method.
9.	Ahlberg, Erik, et al. (författare) "Vi klimatforskare stödjer Greta och skolungdomarna" 2019 Ingår i: Dagens nyheter (DN debatt). - 1101-2447. Tidskriftsartikel (populärvet., debatt m.m.)abstract DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
10.	Akselsson, Cecilia, et al. (författare) Weathering rates in Swedish forest soils 2019 Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 16:22, s. 4429-4450 Forskningsöversikt (refereegranskat)abstract Soil and water acidification was internationally recognised as a severe environmental problem in the late 1960s. The interest in establishing “critical loads” led to a peak in weathering research in the 1980s and 1990s, since base cation weathering is the long-term counterbalance to acidification pressure. Assessments of weathering rates and associated uncertainties have recently become an area of renewed research interest, this time due to demand for forest residues to provide renewable bioenergy. Increased demand for forest fuels increases the risk of depleting the soils of base cations produced in situ by weathering. This is the background to the research programme Quantifying Weathering Rates for Sustainable Forestry (QWARTS), which ran from 2012 to 2019. The programme involved research groups working at different scales, from laboratory experiments to modelling. The aims of this study were to (1) investigate the variation in published weathering rates of base cations from different approaches in Sweden, with consideration of the key uncertainties for each method; (2) assess the robustness of the results in relation to sustainable forestry; and (3) discuss the results in relation to new insights from the QWARTS programme and propose ways to further reduce uncertainties. In the study we found that the variation in estimated weathering rates at single-site level was large, but still most sites could be placed reliably in broader classes of weathering rates. At the regional level, the results from the different approaches were in general agreement. Comparisons with base cation losses after stem-only and whole-tree harvesting showed sites where whole-tree harvesting was clearly not sustainable and other sites where variation in weathering rates from different approaches obscured the overall balance. Clear imbalances appeared mainly after whole-tree harvesting in spruce forests in southern and central Sweden. Based on the research findings in the QWARTS programme, it was concluded that the PROFILE/ForSAFE family of models provides the most important fundamental understanding of the contribution of weathering to long-term availability of base cations to support forest growth. However, these approaches should be continually assessed against other approaches. Uncertainties in the model approaches can be further reduced, mainly by finding ways to reduce uncertainties in input data on soil texture and associated hydrological parameters but also by developing the models, e.g. to better represent biological feedbacks under the influence of climate change.
11.	Albayaty, Muna, et al. (författare) Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study 2017 Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 34:2, s. 560-575 Tidskriftsartikel (refereegranskat)abstract Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that treatment strategies/routines, and hence different treatment preferences, can vary between patients, different stages of opioid maintenance treatment, and countries. This study evaluated the pharmacokinetics and safety of buprenorphine and norbuprenorphine following administration of CAM2038 q1w or q4w versus active controls. Methods: Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone. Results: Eighty-seven subjects were randomized. Median buprenorphine tmax after CAM2038 q4w was 4–10 h (24 h for CAM2038 q1w); mean terminal half-life was 19–25 days (5 days for CAM2038 q1w). CAM2038 q4w showed dose-proportional buprenorphine release, with similar exposure to repeat-dose CAM2038 q1w at comparable monthly dose level. Both CAM2038 formulations showed complete absolute bioavailability of buprenorphine and 5.7- to 7.7-fold greater buprenorphine bioavailability versus sublingual buprenorphine. CAM2038 q1w and q4w were well tolerated; subjects’ acceptance was higher for CAM2038 than for sublingual buprenorphine 1 h post-dose. Conclusions: The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability. Trial registration: ISRCTN24987553. Funding: Camurus AB.
12.	Allen, N, et al. (författare) Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies 2015 Ingår i: The Lancet. Oncology. - 1474-5488. ; 16:9, s. 1061-1070 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women.INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14).FUNDING: Medical Research Council, Cancer Research UK.
13.	Aoude, Lauren G, et al. (författare) Nonsense Mutations in the Shelterin Complex Genes ACD and TERF2IP in Familial Melanoma. 2015 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:2, s. 408-408 Tidskriftsartikel (refereegranskat)abstract The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.
14.	Asp, Håkan, et al. (författare) Slutrapport SLU-Ekoforsk projekt : produktionssystem för ekologisk odling av trädgårdsblåbär 2014 - 2016: organic production systems in Northern highbush blueberries 2017 Rapport (övrigt vetenskapligt/konstnärligt)
15.	Augustinsson, Annelie, et al. (författare) Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer 2018 Ingår i: Acta Oncologica. - 0284-186X. ; 57:5, s. 595-603 Tidskriftsartikel (refereegranskat)abstract Background: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to describe tumor characteristics for each mutation group. Material and methods: Between 1993 and 2013, 231 women who were ≤35 years old when diagnosed with BC were registered at the Oncogenetic Clinic at Skåne University Hospital in Lund, Sweden. Self-reported and registry-reported information regarding first-degree family history of cancer was collected together with information regarding tumor characteristics. Results: Almost perfect agreement was observed between self-reported and registry-reported information regarding first-degree family history of BC (κ = 0.92) and OvC (κ = 0.86). Lesser agreement was observed between reports regarding family history of other types of cancer (κ = 0.51). Mutation screening revealed pathogenic germline mutations in 30.4%; 18.8% in BRCA1, 7.1% in BRCA2 and 4.5% in other genes. Compared with other mutation groups, BRCA1 mutation carriers were more likely to be diagnosed with high-grade, ER-, PR- and triple-negative tumors. Conclusions: Our results demonstrate that physicians and genetic counselors can rely on self-reported information regarding BC and OvC in first-degree relatives. However, self-reported information regarding other types of cancer is not communicated as effectively, and there should be more focus on retrieving the correct information regarding family history of all tumor types. Furthermore, we observed that even though all BC patients fulfilled the criteria for genetic counseling and testing, a large number of patients diagnosed at ≤35 years of age did not receive genetic counseling at the Oncogenetic Clinic. This finding merits further elucidation.
16.	Augustinsson, Annelie, et al. (författare) Cancer in first-degree relatives of women with early-onset breast cancer: a comparison of self-reported and cancer registry data 2016 Ingår i: Cancer Research. - 1538-7445. ; 76:14 Suppl Konferensbidrag (övrigt vetenskapligt/konstnärligt)
17.	Augustinsson, Annelie, et al. (författare) Increasing age at first full-time pregnancy correlates to use of oral contraceptives before age 20 in women with a family history of breast cancer 2015 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
18.	Axelsson, Arvid, et al. (författare) Exploring Multispectral ALS Data for Tree Species Classification 2018 Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 10 Tidskriftsartikel (refereegranskat)abstract Multispectral Airborne Laser Scanning (ALS) is a new technology and its output data have not been fully explored for tree species classification purposes. The objective of this study was to investigate what type of features from multispectral ALS data (wavelengths of 1550 nm, 1064 nm and 532 nm) are best suited for tree species classification. Remote sensing data were gathered over hemi-boreal forest in southern Sweden (58 degrees 2718.35N, 13 degrees 398.03E) on 21 July 2016. The field data consisted of 179 solitary trees from nine genera and ten species. Two new methods for feature extraction were tested and compared to features of height and intensity distributions. The features that were most important for tree species classification were intensity distribution features. Features from the upper part of the upper and outer parts of the crown were better for classification purposes than others. The best classification model was created using distribution features of both intensity and height in multispectral data, with a leave-one-out cross-validated accuracy of 76.5%. As a comparison, only structural features resulted in an highest accuracy of 43.0%. Picea abies and Pinus sylvestris had high user's and producer's accuracies and were not confused with any deciduous species. Tilia cordata was the deciduous species with a large sample that was most frequently confused with many other deciduous species. The results, although based on a small and special data set, suggest that multispectral ALS is a technology with great potential for tree species classification.
19.	Barrett, Jennifer H., et al. (författare) Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions 2015 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6, s. 1351-1360 Tidskriftsartikel (refereegranskat)abstract At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the missing heritability. What's new? In genome-wide association studies, researchers identify genetic variants that frequently associate with a particular disease, though the variants identified may not contribute to the molecular cause of the disease. This study took a closer look at 17 regions associated with melanoma, fine mapping the regions both in people with melanoma and in healthy controls. Though single SNPs account for the association in some regions, they found that in a few regions, several SNPs - and possibly multiple genes - contributed to the association signal. These findings illustrate the importance of not overlooking the interaction between multiple genetic markers when conducting such studies.
20.	Bergström, Ulf, et al. (författare) Stickleback increase in the Baltic Sea - A thorny issue for coastal predatory fish 2015 Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 0272-7714 .- 1096-0015. ; 163, s. 134-142 Tidskriftsartikel (refereegranskat)abstract In the Baltic Sea, the mesopredator three-spined stickleback (Gasterosteus aculeatus) spends a large part of its life cycle in the open sea, but reproduces in shallow coastal habitats. In coastal waters, it may occur in high abundances, is a potent predator on eggs and larvae of fish, and has been shown to induce trophic cascades with resulting eutrophication symptoms through regulation of invertebrate grazers. Despite its potential significance for the coastal food web, little is known about its life history and population ecology. This paper provides a description of life history traits, migration patterns and spatiotemporal development of the species in the Baltic Sea during the past decades, and tests the hypothesis that stickleback may have a negative impact on populations of coastal predatory fish. Offshore and coastal data during the last 30 years show that stickleback has increased fourfold in the Bothnian Sea, 45-fold in the Central Baltic Sea and sevenfold in the Southern Baltic Sea. The abundances are similar in the two northern basins, and two orders of magnitude lower in the Southern Baltic Sea. The coastward spawning migration of sticklebacks from offshore areas peaks in early May, with most spawners being two years of age at a mean length of 65 mm. The early juvenile stage is spent at the coast, whereafter sticklebacks perform a seaward feeding migration in early autumn at a size of around 35 mm. A negative spatial relation between the abundance of stickleback and early life stages of perch and pike at coastal spawning areas was observed in spatial survey data, indicating strong interactions between the species. A negative temporal relationship was observed also between adult perch and stickleback in coastal fish monitoring programmes supporting the hypothesis that stickleback may have negative population level effects on coastal fish predators. The recent increase in stickleback populations in different basins of the Baltic Sea in combination with negative spatiotemporal patterns and previously observed interactions between stickleback and coastal predatory fish suggests that this species may have gained a key role in the coastal food webs of the Baltic Sea. Through its migrations, stickleback may also constitute an important vector linking coastal and open sea ecosystem dynamics. (c) 2015 Elsevier Ltd. All rights reserved.
21.	Betancourt, Lazaro Hiram, et al. (författare) Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data 2019 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
22.	Betancourt, Lazaro Hiram, et al. (författare) The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes 2019 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12 Tidskriftsartikel (refereegranskat)abstract In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
23.	Bohlin, Inka, et al. (författare) Quantifying post-fire fallen trees using multi-temporal lidar 2017 Ingår i: International Journal of Applied Earth Observation and Geoinformation. - : Elsevier BV. - 0303-2434 .- 1569-8432. ; 63, s. 186-195 Tidskriftsartikel (refereegranskat)abstract Massive tree-felling due to root damage is a common fire effect on burnt areas in Scandinavia, but has so far not been analyzed in detail. Here we explore if pre- and post-fire lidar data can be used to estimate the proportion of fallen trees. The study was carried out within a large (14,000 ha) area in central Sweden burnt in August 2014, where we had access to airborne lidar data from both 2011 and 2015. Three data-sets of predictor variables were tested: POST (post-fire lidar metrics), D1F (difference between post- and pre-fire lidar metrics) and combination of those two (POST_DIF). Fractional logistic regression was used to predict the proportion of fallen trees. Training data consisted of 61 plots, where the number of fallen and standing trees was calculated both in the field and with interpretation of drone images. The accuracy of the best model was tested based on 100 randomly selected validation plots with a size of 25 x 25 m.Our results showed that multi-temporal lidar together with field-collected training data can be used for quantifying post-fire tree felling over large areas. Several height-, density- and intensity metrics correlated with the proportion of fallen trees. The best model combined metrics from both datasets (POST DIF), resulting in a RMSE of 0.11. Results were slightly poorer in the validation plots with RMSE of 0.18 using pixel size of 12.5 m and RMSE of 0.15 using pixel size of 6.25 m. Our model performed least well for stands that had been exposed to high-intensity crown fire. This was likely due to the low amount of echoes from the standing black tree skeletons. Wall-to-wall maps produced with this model can be used for landscape level analysis of fire effects and to explore the relationship between fallen trees and forest structure, soil type, fire intensity or topography.
24.	Borgquist, Signe, et al. (författare) Statin use and breast cancer survival - A Swedish nationwide study 2019 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background: A sizeable body of evidence suggests that statins can cease breast cancer progression and prevent breast cancer recurrence. The latest studies have, however, not been supportive of such clinically beneficial effects. These discrepancies may be explained by insufficient power. This considerably sized study investigates the association between both pre- and post-diagnostic statin use and breast cancer outcome. Methods: A Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer related death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality. Results: During a median follow-up time of 61.6 months, a total of 4678 patients died, of which 2669 were considered breast cancer related deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer related deaths (HR = 0.77; 95% CI 0.63-0.95, P = 0.014). Similarly, post-diagnostic statin use compared to non-use was associated with lower risk of breast cancer related deaths (HR = 0.83; 95% CI 0.75-0.93, P = 0.001). Conclusion: This study supports the notion that statin use is protective regarding breast cancer related mortality in agreement with previous Scandinavian studies, although less so with studies in other populations. These disparities should be further investigated to pave the way for future randomized clinical trials investigating the role of statins in breast cancer.
25.	Boström, Lena, 1960-, et al. (författare) Digital visualisering i skolan : Mittuniversitetets slutrapport från förstudien 2018 Rapport (övrigt vetenskapligt/konstnärligt)abstract Den här studiens syfte har varit tvåfaldigt, nämligen att testa alternativa lärmetoder via ett digitalt läromedel i matematik i en kvasiexperimentell studie samt att tillämpa metoder av användarupplevelser för interaktiva visualiseringar, och därigenom öka kunskapen kring hur upplevd kvalitet beror på använd teknik. Pilotstudien sätter också fokus på flera angelägna områden inom skolutveckling både regionalt och nationellt samt viktiga aspekter när det gäller kopplingen teknik, pedagogik och utvärderingsmetoder inom “den tekniska delen”. Det förra handlar om sjunkande matematikresultat i skolan, praktiknära skolforskning, stärkt digital kompetens, visualisering och lärande samt forskning om visualisering och utvärdering. Den senare svarar på frågor om vilka tekniska lösningar som tidigare använts och med vilket syfte har de skapats samt hur visualiseringar har utvärderats enligt läroböcker och i forskningslitteratur. När det gäller elevernas resultat, en av de stora forskningsfrågorna i studien, så fann vi inga signifikanta skillnader mellan traditionell undervisning och undervisning med visualiseringsläromedlet (3D). Beträffande elevers attityder till matematikmomentet kan konstateras att i kontrollgruppen för årskurs 6 förbättrades attityden signifikans, men inte i klass 8. Gällande flickors och pojkars resultat och attityder kan vi konstatera att flickorna i båda klasserna hade bättre förkunskaper än pojkarna samt att i årskurs 6 var flickorna mer positiva till matematikmomentet än pojkarna i kontrollgruppen. Därutöver kan vi inte skönja några signifikanta skillnader. Andra viktiga rön i studien var att provkonstruktionen inte var optimal samt att tiden för provgenomförande har stor betydelse när på dagen det genomfördes. Andra resultat resultaten i den kvalitativa analysen pekar på positiva attityder och beteenden från eleverna vid arbetet med det visuella läromedlet. Elevernas samarbete och kommunikation förbättrades under lektionerna. Vidare pekade lärarna på att med 3D-läromedlet gavs större möjligheter till att stimulera flera sinnen under lärprocessen. En tydlig slutsats är att 3D-läromedlet är ett viktigt komplement i undervisningen, men kan inte användas helt självt. Vi kan varken sälla oss till de forskare som anser att 3D-visualisering är överlägset som läromedel för elevers resultat eller till de forskare som varnar för dess effekter för elevers kognitiva överbelastning. Våra resultat ligger mer i linje med de slutsatser Skolforskningsinstitutet (2017) drar, nämligen att undervisning med digitala läromedel i matematik kan ha positiva effekter, men en lika effektiv undervisning kan möjligen designas på andra sätt. Däremot pekar resultaten i vår studie på ett flertal störningsmoment som kan ha påverkat möjliga resultat och behovet av god teknologin och välutvecklade programvaror. I studien har vi analyserat resultaten med hjälp av två övergripande ramverk för integrering av teknikstöd i lärande, SAMR och TPACK. Det förra ramverket bidrog med en taxonomi vid diskussionen av hur väl teknikens möjligheter tagits tillvara av läromedel och i läraktiviteter, det senare för en diskussion om de didaktiska frågeställningarna med fokus på teknikens roll. Båda aspekterna är högaktuella med tanke på den ökande digitaliseringen i skolan. Utifrån tidigare forskning och denna pilotstudie förstår vi att det är viktigt att designa forskningsmetoderna noggrant. En randomisering av grupper vore önskvärt. Prestandamått kan också vara svåra att välja. Tester där personer får utvärdera användbarhet (usability) och användarupplevelse (user experience, UX) baserade på både kvalitativa och kvantitativa metoder blir viktiga för själva användandet av tekniken, men det måste till ytterligare utvärderingar för att koppla tekniken och visualiseringen till kvaliteten i lärandet och undervisningen. Flera metoder behövs således och det blir viktigt med samarbete mellan olika ämnen och discipliner.
26.	Burden, Håkan, et al. (författare) Accelerating Acquisition in an Open Innovation Ecosystem 2019 Ingår i: Proc of Twenty-fifth Americas Conference on Information Systems. Konferensbidrag (refereegranskat)abstract Maritime transports are to be regarded as a self-organized ecosystem (Kay et al., 1999) characterized by sub-optimization where historically each actor to has optimized its own operations, often giving rise to inefficiencies as a whole. In recent years however, digital transformation has challenged this by providing means for enhanced transparency in data sharing and situational awareness, enabling better coordination and improved efficiency on the whole (Lind et al. 2018a). Digital transformation drives the possibilities of creating new value by enabling higher degrees of connectivity between actors, digitally twin physical objects, drawing patterns of behaviour based on extensive sets of historical data, as well as harmonizing data sharing through standardized interfaces and communication protocols (e.g. Almirall and Casadesus-Masanell 2010; Gassman et al. 2010; Lakhani et al. 2006). To break existing patterns of behaviour and to avoid the creation of proprietary solutions that feed sub-optimization, there is a need for new inspiration and perspectives that capitalize on the opportunities that digital transformation provides. From an open innovation point of view, this means that innovators both having experience from the sector as well as from other sectors would come together, come up with, and provide new applications not previously possible or never thought about before. A core capability that the ecosystem needs to develop and ensure is data streams made accessible for those that can provide new applications aimed for the single actor and/or clusters of actors, within or outside the maritime sector (Lind et al. 2018).This has also been one of the objectives for Port Collaborative Decision Making (PortCDM), which is a concept that provides guidelines and standards for the data exchange within and between ports, between ships and ports, and between ports and hinterland operators (Lind et al 2018). Such data exchange is necessary if enhanced efficiency during port call operations is to be achieved but also facilitates open innovation within the maritime sector. In order to realise that potential, a purposive transfer of knowledge between the established actors and potential new service providers has to be established (Chesbrough 2006). We therefore set out to explore How can open innovation intermediaries accelerate acquisition in an ecosystem through the management and throughput of knowledge transfer?We address the question through a longitudinal study by applying an action research approach involving actors from the local port and students from three bachelor programs. Before we describe the specifics of the research methodology, we outline our theoretical framework in terms of how knowledge transfer can be framed within an open innovation ecosystem. After the research methodology we detail the five iterations and then discuss the effect on knowledge transfer within the ecosystem. Finally, we conclude and give directions on future research.
27.	Byberg, Liisa, et al. (författare) Reply to WB Grant 2017 Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 106:2, s. 700-701 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
28.	Byberg, Liisa, et al. (författare) Reply to Y Mao and H Yu. 2017 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 106:2, s. 698-699 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
29.	Candido-dos-Reis, Francisco J, et al. (författare) Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer 2015 Ingår i: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652 Tidskriftsartikel (refereegranskat)abstract PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
30.	Caspillo, Nasim Reyhanian, 1982- (författare) Hitting the mark : studies of alterations in behaviour and fertility in ethinyl estradiol-exposed zebrafish and search related biomarkers 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract In this thesis, we have analysed the effects of EE2 on non-reproductive behaviours and fertility. We have showed that two doses of EE2 in male adult short-term exposures evokes opposite behaviours in the novel tank test. A lower dose induced increased bottom-dwelling, a sign of increased anxiety and a higher dose increased surface-dwelling, which would likely expose themselves to predation in a natural environment. Increased shoaling was observed in both exposures, possibly affecting feeding and reproduction opportunities. Fertility analysis of these fish demonstrated a complete inhibition of spawning in the highest dose group. To investigate mechanisms behind the spawning failure, we examined expression levels of genes involved in zebrafish sex differentiation and maintenance of gonadal function. We found downregulated transcription levels of male-predominant genes, suggesting a demasculinization of the testes contributing to functional sterility in these fish. We have demonstrated that non-reproductive behaviour in zebrafish is highly sensitive to EE2 exposure during development. After exposing male and female zebrafish to low doses of EE2 followed by remediation in clean water until adulthood, the fish displayed increased anxiety and shoaling behaviour, demonstrating persistent effects of EE2. Furthermore, behavioural effects were transferred to their progeny. Decreased fertilisation success of the developmentally exposed fish was observed in both sexes when mated to untreated animals of the opposite sex. These fertility effects persisted although the fish had a long remediation period, implying likely reduced fitness of fish populations in aquatic environments. Based on our findings on non-reproductive behaviours and fertility, we performed RNAsequencing analysis of the brain and testes in order to investigate possible biological mechanisms behind the persistent effects. There is a need for biomarkers allowing detection of both reversible and irreversible effects in animals exposed to estrogenic substances, hopefully contributing to better risk assessments for EDCs. Results from RNA-sequencing would serve as a basis for continued studies in pursuit of potential biomarkers.
31.	Christensen, Gustav Boelsgaard, et al. (författare) Sunbed Use Increases Cutaneous Squamous Cell Carcinoma Risk in Women : A Large-scale, Prospective Study in Sweden 2019 Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 99:10, s. 878-883 Tidskriftsartikel (refereegranskat)abstract The incidence of cutaneous squamous cell carcinoma has increased rapidly in Sweden in the past decades. Here, we present a prospective study of the Melanoma in Southern Sweden (MISS)-cohort, with 29,460 participating women in southern Sweden that investigates the risk factors for cutaneous squamous cell carcinoma. Data on the host and skin cancer risk factors were collected through questionnaires and then matched with the National Cancer Registry. Statistical analyses were based on uni- and multivariable Cox proportional hazards models, using age as the time-scale. We found that sunbed use (hazard ratio (HR) 1.2, 95% CI: 1.1-1.4), red and light blond hair (HR 1.6, 95% CI: 1.1-2.3), freckles (HR 1.4, 95% CI: 1.1-1.8) and immunosuppressive medications (HR 2.1, 95% CI: 1.3-4.5) were independent risk factors. Furthermore, we observed a dose-dependent relationship between sunbed use and the development of cutaneous squamous cell carcinoma. Our findings support the idea of integrating dermatological follow-up examinations for immunosuppressed patients and banning the use of sunbeds in order to prevent cutaneous squamous cell carcinoma.
32.	Cirenajwis, Helena, et al. (författare) Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy. 2015 Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309 Tidskriftsartikel (refereegranskat)abstract Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
33.	Cirenajwis, Helena, et al. (författare) NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics 2017 Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 11:4, s. 438-451 Tidskriftsartikel (refereegranskat)abstract In general, melanoma can be considered as a UV-driven disease with an aggressive metastatic course and high mutational load, with only few tumors (acral, mucosal, and uveal melanomas) not induced by sunlight and possessing a lower mutational load. The most commonly activated pathway in melanoma is the mitogen-activated protein kinase (MAPK) pathway. However, the prognostic significance of mutational stratification is unclear and needs further investigation. Here, in silico we combined mutation data from 162 melanomas subjected to targeted deep sequencing with mutation data from three published studies. Tumors from 870 patients were grouped according to BRAF, RAS, NF1 mutation or triple-wild-type status and correlated with tumor and patient characteristics. We found that the NF1-mutated subtype had a higher mutational burden and strongest UV mutation signature. Searching for co-occurring mutated genes revealed the RASopathy genes PTPN11 and RASA2, as well as another RAS domain-containing gene RASSF2 enriched in the NF1 subtype after adjustment for mutational burden. We found that a larger proportion of the NF1-mutant tumors were from males and with older age at diagnosis. Importantly, we found an increased risk of death from melanoma (disease-specific survival, DSS; HR, 1.9; 95% CI, 1.21-3.10; P = 0.046) and poor overall survival (OS; HR, 2.0; 95% CI, 1.28-2.98; P = 0.01) in the NF1 subtype, which remained significant after adjustment for age, gender, and lesion type (DSS P = 0.03, OS P = 0.06, respectively). Melanoma genomic subtypes display different biological and clinical characteristics. The poor outcome observed in the NF1 subtype highlights the need for improved characterization of this group.
34.	Cook, Michael B, et al. (författare) Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium. 2015 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531 Tidskriftsartikel (refereegranskat)abstract Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
35.	Davies, John R, et al. (författare) Development and validation of a melanoma risk score based on pooled data from 16 case-control studies 2015 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:5, s. 24-817 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: We report the development of a cutaneous melanoma risk algorithm based upon seven factors; hair color, skin type, family history, freckling, nevus count, number of large nevi, and history of sunburn, intended to form the basis of a self-assessment Web tool for the general public.METHODS: Predicted odds of melanoma were estimated by analyzing a pooled dataset from 16 case-control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th, and 90th centiles were used to distribute individuals into four risk groups for their age, sex, and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case-control study dataset.RESULTS: Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset [area under the curve, 0.75; 95% confidence interval (CI), 0.73-0.78]. Twenty-nine percent of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases.CONCLUSION: We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset.IMPACT: This score may be a useful tool to inform members of the public about their melanoma risk.
36.	Degerman, Erik, et al. (författare) Fisk som miljöindikator 2016 Rapport (övrigt vetenskapligt/konstnärligt)abstract Här presenteras en kort genomgång av hur fisk används som miljöindikator i vårt arbete med miljöövervakning vid institutionen för akvatiska resurser på Sveriges lantbruksuniversitet. Rapporten behandlar både sötvatten, kust och hav. I rapporten går vi igenom de undersökningsmetoder vi använder och hur och varför fisk reagerar på olika typer av miljöpåverkan. Vi berör närmare effekter av försurning, övergödning, klimatförändringar, miljögifter, främmande arter, vattenkraft och annan fysisk påverkan på miljön. Effekten av för hårt fiske kan naturligtvis också tydligt ses på drabbade fiskbestånd, till exempel genom en förändrad storleksoch åldersstruktur, svag föryngring eller få lekfiskar. Fisken indikerar således både resursutnyttjandet och miljötillståndet. Fisk är en bra indikator, till stor del därför att vi väl känner till vad som är normalt - hur mycket och vilka arter som bör förekomma, hur de tillväxer, vilken variation i arvsmassan de har, hur gamla de brukar bli, vart de vandrar och vilka mängder av miljögifter de brukar innehålla. Dessutom är det organismer som allmänheten känner till och därför kan man enkelt kommunicera miljöproblem med hjälp av fisk, samtidigt som allmänheten genom sitt intresse kan rapportera in sina egna observationer. En viktig komponent är också att vi på uppdrag av Havs- och vattenmyndigheten och flera av våra länsstyrelser genomför omfattande provfisken över hela landet med standardiserade metoder. Kunskapen om vad som är normalt och vad som händer när ett vatten påverkas ökar därför hela tiden.
37.	Dork, T, et al. (författare) Two truncating variants in FANCC and breast cancer risk 2019 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524- Tidskriftsartikel (refereegranskat)abstract Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
38.	Duffy, David L., et al. (författare) Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways 2018 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1-10 Tidskriftsartikel (refereegranskat)abstract The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis. © 2018, The Author(s).
39.	Egberth, Mikael, et al. (författare) Combining airborne laser scanning and Landsat data for statistical modeling of soil carbon and tree biomass in Tanzanian Miombo woodlands 2017 Ingår i: Carbon Balance and Management. - : BioMed Central (BMC). - 1750-0680. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Soil carbon and biomass depletion can be used to identify and quantify degraded soils,and by using remote sensing, there is potential to map soil conditions over large areas.Landsat 8 Operational Land Imager satellite data and airborne laser scanning datawere evaluated separately and in combination for modeling soil organic carbon, aboveground tree biomass and below ground tree biomass. The test site is situated in theLiwale district in southeastern Tanzania and is dominated by Miombo woodlands. Treedata from 15m radius field-surveyed plots and samples of soil carbon down to a depthof 30cm were used as reference data for tree biomass and soil carbon estimations.Cross-validated plot level error (RMSE) for predicting soil organic carbon was 28%using only Landsat 8, 26% using laser only, and 23% for the combination of the two.The plot level error for above ground tree biomass was 66% when using only Landsat8, 50% for laser and 49% for the combination of Landsat 8 and laser data. Results forbelow ground tree biomass were similar to above ground biomass. Additionally it wasfound that an early dry season satellite image was preferable for modelling biomasswhile images from later in the dry season were better for modelling soil carbon.The results show that laser data is superior to Landsat 8 when predicting both soilcarbon and biomass above and below ground in landscapes dominated by Miombowoodlands. Furthermore, the combination of laser data and Landsat data weremarginally better than using laser data only.
40.	Ehlers, Sarah, et al. (författare) Assessing Error Correlations in Remote Sensing-Based Estimates of Forest Attributes for Improved Composite Estimation 2018 Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 10 Tidskriftsartikel (refereegranskat)abstract Today, non-expensive remote sensing (RS) data from different sensors and platforms can be obtained at short intervals and be used for assessing several kinds of forest characteristics at the level of plots, stands and landscapes. Methods such as composite estimation and data assimilation can be used for combining the different sources of information to obtain up-to-date and precise estimates of the characteristics of interest. In composite estimation a standard procedure is to assign weights to the different individual estimates inversely proportional to their variance. However, in case the estimates are correlated, the correlations must be considered in assigning weights or otherwise a composite estimator may be inefficient and its variance be underestimated. In this study we assessed the correlation of plot level estimates of forest characteristics from different RS datasets, between assessments using the same type of sensor as well as across different sensors. The RS data evaluated were SPOT-5 multispectral data, 3D airborne laser scanning data, and TanDEM-X interferometric radar data. Studies were made for plot level mean diameter, mean height, and growing stock volume. All data were acquired from a test site dominated by coniferous forest in southern Sweden. We found that the correlation between plot level estimates based on the same type of RS data were positive and strong, whereas the correlations between estimates using different sources of RS data were not as strong, and weaker for mean height than for mean diameter and volume. The implications of such correlations in composite estimation are demonstrated and it is discussed how correlations may affect results from data assimilation procedures.
41.	Ekedahl, Henrik, et al. (författare) High TERT promoter mutation frequency in non-acral cutaneous metastatic melanoma 2016 Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 29:5, s. 598-600 Tidskriftsartikel (refereegranskat)
42.	Ellberg, Carolina, et al. (författare) Current smoking is associated with a larger waist circumference and a more androgenic profile in young healthy women from high-risk breast cancer families 2018 Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 29:2, s. 243-251 Tidskriftsartikel (refereegranskat)abstract The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5–10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.
43.	Ellberg, Carolina, et al. (författare) Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort. 2015 Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 54:1, s. 39-50 Tidskriftsartikel (refereegranskat)abstract Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
44.	Escala-Garcia, M, et al. (författare) Genome-wide association study of germline variants and breast cancer-specific mortality 2019 Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 120:6, s. 647-657 Tidskriftsartikel (refereegranskat)
45.	Falk, Hilda, et al. (författare) Sju procent av cancerfallen hade "missats" vid kolonundersökning - 22 av 307 patienter i Västerbotten hade fått kolon undersökt 5 år-3 månader före diagnosen kolorektal cancer : [How many patients had their colon investigated within five years prior to colorectal cancer diagnosis?] 2018 Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 115:40 Tidskriftsartikel (refereegranskat)abstract We aimed to investigate the prevalence of patients who had their colon investigated five years to three months before their colorectal cancer (CRC) was diagnosed. All patients diagnosed between January 1st 2016 and September 14th 2017 in the county of Västerbotten, Sweden were included (n=307). The proportion of patients with CRC who had their colon investigated before diagnosis was 7% (n=22). The median time from the index examination to the date of diagnosis of CRC was 1013 days (IQR 639 days). In addition, 16% of the patients had a positive FIT test (F-Hb) and 23% had anemia that was known more than three months prior to diagnosis. A long duration of anemia before diagnosis was significantly more common in men than in women (31% vs 16%; p=0.003). We conclude that the incidence of “missed” CRC are low but may be improved by a thorough adherence to colonoscopy guidelines. We found that a positive iFOBT and anemia often were detected more than three months prior to diagnosis.
46.	Fang, Jun, et al. (författare) Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148 2017 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Tidskriftsartikel (refereegranskat)abstract Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
47.	Fava, Cristiano, et al. (författare) A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study 2015 Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23, s. 969-974 Tidskriftsartikel (refereegranskat)abstract Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors’, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
48.	Ferreira, MA, et al. (författare) Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer 2019 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741- Tidskriftsartikel (refereegranskat)abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
49.	Figlioli, G, et al. (författare) The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer 2019 Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38- Tidskriftsartikel (refereegranskat)abstract Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658, p.Gln1701, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
50.	Fohlin, Helena, 1979- (författare) Long-term prognostic and predictive factors in hormone receptor positive breast cancer 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The breast cancer survival in Sweden is good (almost 90 % 5-year relative survival) and has increased over time. For women with hormone receptor negative tumors, most relapses occur within the first 5 years after diagnosis. Thereafter the recurrence risk decreases rapidly. For women with estrogen receptor positive (ER+) tumors the annual risk for late recurrences is 1 – 2 %, even after 5 years of endocrine therapy. This risk accumulates so that approximately 25 % of the patients that are recurrence-free after five years from diagnosis may experience a relapse within further 15 years of follow-up. The relatively high long-term risk calls for identification of prognostic and predictive markers with long-term effect. Though, the number of such markers with proven significance is limited. Of the clinical characteristics, only nodal status and to some extent tumor size and tumor grade have been shown to have long-term prognostic value. In this thesis, we propose long-term prognostic and predictive markers for breast cancer.In paper I, we suggest the protein v-akt murine thymoma viral oncogene homologue 2 (AKT2) as a long-term prognostic marker among patients with ER+ tumors. In our study, besides nodal status, AKT2 was the only factor with long-term prognostic value. This is in accordance with some other studies, though we also showed that the significance of AKT2 was limited to ER+ tumors and that the impact increased with higher ER expression.Approximately 75 – 85 % of the ER+ tumors are also progesterone receptor positive (PR+). ER+/progesterone receptor negative (PR-) tumors are considered to be more aggressive and patients with such tumors are often treated with chemotherapy. In this group, more specific subgroups for targeted therapy are needed.Whereas ER has long been established as a predictive factor regarding tamoxifen benefit, the role of PR has not been clarified to date. In paper II, we showed that PR status adds predictive value to ER considering the long-term benefit from tamoxifen.In paper III, we aimed to identify new prognostic markers among patients with ER+ tumors. Systemically untreated patients with ER+/PR- tumors and high expression of the Ras-related protein RAB6C (RAB6C) had reduced distant recurrence rate. Therefore, we suggest RAB6C as a candidate marker for subgroup division among patients with ER+/PR- tumors.According to the results from paper II, there might be subgroups of patients with ER+/PRtumors that do benefit from tamoxifen. The aim of paper IV was to identify such subgroups. Here, we suggest that patients with ER+/PR- tumors and low RAB6C expression do benefit from tamoxifen.The results from this thesis may encourage further studies for more specific subgroup divisions. Such studies may lead to changes in the management program, where some patients with ER+ tumors should receive prolonged or more intense treatment and others reduced treatment based on the pathological markers AKT2, PR and RAB6C.

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