| 1. |
|
|
| 2. |
- Coviello, Andrea D, et al.
(författare)
-
A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
-
Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
|
|
| 3. |
- Howe, LJ, et al.
(författare)
-
Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:65, s. 581-
-
Tidskriftsartikel (refereegranskat)abstract
- Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Wettermark, B., et al.
(författare)
-
The Nordic prescription databases as a resource for pharmacoepidemiological researcha literature review
- 2013
-
Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 22:7, s. 691-699
-
Forskningsöversikt (refereegranskat)abstract
- Purpose All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. Methods The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. Results A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. Conclusions The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up. Copyright (c) 2013 John Wiley & Sons, Ltd.
|
|
| 7. |
- Abbott, Benjamin W., et al.
(författare)
-
Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
|
|
| 8. |
|
|
| 9. |
- Alvarez, J. L., et al.
(författare)
-
Educational inequalities in tuberculosis mortality in sixteen European populations
- 2011
-
Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 15:11, s. 1461-1467
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe the magnitude of socioeconomic inequalities in tuberculosis (TB) mortality by level of education in male, female, urban and rural populations in several European countries. DESIGN: Data were obtained from the Eurothine Project, covering 16 populations between 1990 and 2003. Age- and sex-standardised mortality rates, the relative index of inequality and the slope index of inequality were used to assess educational inequalities. RESULTS: The number of TB deaths reported was 8530, with a death rate of 3 per 100000 per year, of which 73% were males. Educational inequalities in TB mortality were present in all European populations. Inequalities in TB mortality were greater than in total mortality. Relative and absolute inequalities were large in Eastern European and Baltic countries but relatively small in Southern European countries and in Norway, Finland and Sweden. Inequalities in mortality were observed among both men and women, and in both rural and urban populations. CONCLUSIONS: Socio-economic inequalities in TB mortality exist in all European countries. Firm political commitment is required to reduce inequalities in the social determinants of TB incidence. Targeted public health measures are called for to improve access to treatment of vulnerable groups and thereby reduce TB mortality.
|
|
| 10. |
- Christensen, Torben, et al.
(författare)
-
Factors controlling large scale variations in methane emissions from wetlands
- 2003
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 30:7
-
Tidskriftsartikel (refereegranskat)abstract
- [1] Global wetlands are, at estimate ranging 115-237 Tg CH4/yr, the largest single atmospheric source of the greenhouse gas methane (CH4). We present a dataset on CH4 flux rates totaling 12 measurement years at sites from Greenland, Iceland, Scandinavia and Siberia. We find that temperature and microbial substrate availability (expressed as the organic acid concentration in peat water) combined explain almost 100% of the variations in mean annual CH4 emissions. The temperature sensitivity of the CH4 emissions shown suggests a feedback mechanism on climate change that could validate incorporation in further developments of global circulation models.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Illana, A., et al.
(författare)
-
Coulomb excitation of 74,76Zn
- 2023
-
Ingår i: Physical Review C. - 2469-9985. ; 108:4
-
Tidskriftsartikel (refereegranskat)abstract
- The first experiment using radioactive beams post-accelerated by the HIE-ISOLDE facility has enabled to obtain a precise set of B(E2) transition probabilities in neutron-rich 74,76Zn isotopes. The resulting B(E2; 2+1→0+1) values are consistent with those determined in earlier REX-ISOLDE measurements. While the B(E2; 4+1→2+1) transition probability in 76Zn is also in agreement with earlier Coulomb-excitation results, the value obtained for 74Zn is considerably lower. For the first time, a spectroscopic quadrupole moment of the 2+1 state was measured for an exotic nucleus in this mass region. A detailed comparison is presented with large-scale shell-model and Monte Carlo shell-model calculations.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Bekkhus, Tove, et al.
(författare)
-
Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
|
|
| 18. |
- Borrell, C, et al.
(författare)
-
Socioeconomic inequalities in mortality in 16 European cities
- 2014
-
Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 42:3, s. 245-254
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To explore inequalities in total mortality between small areas of 16 European cities for men and women, as well as to analyse the relationship between these geographical inequalities and their socioeconomic indicators. Methods: A cross-sectional ecological design was used to analyse small areas in 16 European cities (26,229,104 inhabitants). Most cities had mortality data for a period between 2000 and 2008 and population size data for the same period. Socioeconomic indicators included an index of socioeconomic deprivation, unemployment, and educational level. We estimated standardised mortality ratios and controlled for their variability using Bayesian models. We estimated relative risk of mortality and excess number of deaths according to socioeconomic indicators. Results: We observed a consistent pattern of inequality in mortality in almost all cities, with mortality increasing in parallel with socioeconomic deprivation. Socioeconomic inequalities in mortality were more pronounced for men than women, and relative inequalities were greater in Eastern and Northern European cities, and lower in some Western (men) and Southern (women) European cities. The pattern of excess number of deaths was slightly different, with greater inequality in some Western and Northern European cities and also in Budapest, and lower among women in Madrid and Barcelona. Conclusions: In this study, we report a consistent pattern of socioeconomic inequalities in mortality in 16 European cities. Future studies should further explore specific causes of death, in order to determine whether the general pattern observed is consistent for each cause of death.
|
|
| 19. |
- Brandao, Luiz Eduardo M., et al.
(författare)
-
Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial
- 2022
-
Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:2
-
Tidskriftsartikel (refereegranskat)abstract
- The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (similar to 27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
|
|
| 20. |
- Capek, P. T., et al.
(författare)
-
A plant-microbe interaction framework explaining nutrient effects on primary production
- 2018
-
Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:10, s. 1588-1596
-
Tidskriftsartikel (refereegranskat)abstract
- In most terrestrial ecosystems, plant growth is limited by nitrogen and phosphorus. Adding either nutrient to soil usually affects primary production, but their effects can be positive or negative. Here we provide a general stoichiometric framework for interpreting these contrasting effects. First, we identify nitrogen and phosphorus limitations on plants and soil microorganisms using their respective nitrogen to phosphorus critical ratios. Second, we use these ratios to show how soil microorganisms mediate the response of primary production to limiting and non-limiting nutrient addition along a wide gradient of soil nutrient availability. Using a meta-analysis of 51 factorial nitrogen-phosphorus fertilization experiments conducted across multiple ecosystems, we demonstrate that the response of primary production to nitrogen and phosphorus additions is accurately predicted by our stoichiometric framework. The only pattern that could not be predicted by our original framework suggests that nitrogen has not only a structural function in growing organisms, but also a key role in promoting plant and microbial nutrient acquisition. We conclude that this stoichiometric framework offers the most parsimonious way to interpret contrasting and, until now, unresolved responses of primary production to nutrient addition in terrestrial ecosystems.
|
|
| 21. |
- Christensen, Torben R., et al.
(författare)
-
Large scale variations in CH4 emissions from wetlands explained by temperature and substrate availability
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Globally, wetlands are at estimates ranging 115-237 Tg C4/yr1 the largest single source of the greenhouse gas CH4 to the atmosphere. Important feedback mechanisms on climate change arising from changing exchanges of C02 between the terrestrial biosphere and the atmosphere have recently been identified2. A related question is how will possible changes in the CH4 emissions from wetlands affect the further development of the greenhouse effect? Here we show using comparable methods in a wide range of wetlands ranging from Greenland to Siberia that regardless the dependency on soil moisture, plant productivity and other factors, temperature is the strongest control and predictor of CH4 emissions across both temporal and large spatial scales. Furthermore, we show that CH4 flux variations not explained by temperature can beattributed to differences in microbial substrate availability (expressed as the organic acid concentration in peat water). Combined, soil temperature and organic acid concentrations explains 99% of the variation in CH4 fluxes between the different sites. The temperature sensitivity of the CH4 emissions shown suggests a strong feedback mechanism on climatechange that should valid incorporation in developments of global circulation models.
|
|
| 22. |
- Gadeyne, S, et al.
(författare)
-
The turn of the gradient? Educational differences in breast cancer mortality in 18 European populations during the 2000s
- 2017
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 141:1, s. 33-44
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to investigate the association between educational level and breast cancer mortality in Europe in the 2000s. Unlike most other causes of death, breast cancer mortality tends to be positively related to education, with higher educated women showing higher mortality rates. Research has however shown that the association is changing from being positive over non-existent to negative in some countries. To investigate these patterns, data from national mortality registers and censuses were collected and harmonized for 18 European populations. The study population included all women aged 30-74. Age-standardized mortality rates, mortality rate ratios, and slope and relative indexes of inequality were computed by education. The population was stratified according to age (women aged 30-49 and women aged 50-74). The relation between educational level and breast cancer mortality was predominantly negative in women aged 30-49, mortality rates being lower among highly educated women and higher among low educated women, although few outcomes were statistically significant. Among women aged 50-74, the association was mostly positive and statistically significant in some populations. A comparison with earlier research in the 1990s revealed a changing pattern of breast cancer mortality. Positive educational differences that used to be significant in the 1990s were no longer significant in the 2000s, indicating that inequalities have decreased or disappeared. This evolution is in line with the "fundamental causes" theory which stipulates that whenever medical insights and treatment become available to combat a disease, a negative association with socio-economic position will arise, independently of the underlying risk factors.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Havukainen, Martti, et al.
(författare)
-
A Case Study on Co-designing Digital Games with Older Adults and Children : Game Elements, Assets, and Challenges
- 2020
-
Ingår i: The Computer Games Journal. - : Springer. - 2052-773X. ; 9:2, s. 163-188
-
Tidskriftsartikel (refereegranskat)abstract
- Digital games have traditionally been targeted at younger generations, although the proportion of older adult players is increasing. However, the design processes of digital games often do not consider the special needs of older adults. Co-design is a potential method to address this, but there is little research on co-designing games with older adults. In our study, we proposed a co-design process model that considers the intergenerational perspective. Using this model, eight older adults (two males and six females aged 47–80) and 22 sixth graders (11 males and 11 females aged 12–13) co-designed a digital game. The content of the game was based on old concepts used by the designers during their childhood. Similarly, game content involving new words and concepts were produced by the sixth graders. We collected data using semi-structured interviews and observations during the co-design process over a period of 24 months and then processed the data using grounded theory. The results indicated that the older adults identified seven game elements as essential to make games fun—appearance and aesthetics, competition, manageability of gameplay, social impact, familiarity, unpredictability, and intergenerational gameplay. Furthermore, we identified six assets that older adults have as game co-designers and five challenges that co-designing games with older adults may entail.
|
|
