| 1. |
- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 2. |
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| 3. |
- Bakken, TE, et al.
(author)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Journal article (peer-reviewed)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 4. |
- Gonzalez, C. A., et al.
(author)
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Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:5, s. 1320-1324
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Journal article (peer-reviewed)abstract
- In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII((R))). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.
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| 5. |
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| 6. |
- Tsilidis, K. K., et al.
(author)
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Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2011
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In: British Journal of Cancer. - London : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 105:9, s. 1436-1442
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs <= 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors. British Journal of Cancer (2011) 105, 1436-1442. doi:10.1038/bjc.2011.371 www.bjcancer.com Published online 13 September 2011 (C) 2011 Cancer Research UK
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| 7. |
- Tsilidis, K. K., et al.
(author)
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Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
- 2010
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:11, s. 1755-1759
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Journal article (peer-reviewed)abstract
- BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. British Journal of Cancer (2010) 103, 1755-1759. doi:10.1038/sj.bjc.6605965 www.bjcancer.com Published online 2 November 2010 (C) 2010 Cancer Research UK
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| 8. |
- Hellsten, Sofie, et al.
(author)
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Abating N in Nordic agriculture – policy, measures and way forward
- 2019
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In: Journal of Environmental Management. - 0301-4797 .- 1095-8630. ; 236, s. 674-686
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Journal article (peer-reviewed)abstract
- During the past twenty years, the Nordic countries (Denmark, Sweden, Finland and Norway) have introduced a range of measures to reduce losses of nitrogen (N) to air and to aquatic environment by leaching and runoff. However, the agricultural sector is still an important N source to the environment, and projections indicate relatively small emission reductions in the coming years. The four Nordic countries have different priorities and strategies regarding agricultural N flows and mitigation measures, and therefore they are facing different challenges and barriers. In Norway farm subsidies are used to encourage measures, but these are mainly focused on phosphorus (P). In contrast, Denmark targets N and uses control regulations to reduce losses. In Sweden and Finland, both voluntary actions combined with subsidies help to mitigate both N and P. The aim of this study was to compare the present situation pertaining to agricultural N in the Nordic countries as well as to provide recommendations for policy instruments to achieve cost effective abatement of reactive N from agriculture in the Nordic countries, and to provide guidance to other countries. To further reduce N losses from agriculture, the four countries will have to continue to take different routes. In particular, some countries will need new actions if 2020 and 2030 National Emissions Ceilings Directive (NECD) targets are to be met. Many options are possible, including voluntary action, regulation, taxation and subsidies, but the difficulty is finding the right balance between these policy options for each country. The governments in the Nordic countries should put more attention to the NECD and consult with relevant stakeholders, researchers and farmer's associations on which measures to prioritize to achieve these goals on time. It is important to pick remaining low hanging fruits through use of the most cost effective mitigation measures. We suggest that N application rate and its timing should be in accordance with the crop need and carrying capacity of environmental recipients. Also, the choice of application technology can further reduce the risk of N losses into air and waters. This may require more region-specific solutions and knowledge-based support with tailored information in combination with further targeted subsidies or regulations.
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| 9. |
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| 10. |
- Smith, K.A., et al.
(author)
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Oxidation of atmospheric methane in Northern European soils, comparison with other ecosystems, and uncertainties in the global terrestrial sink
- 2000
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 6:7, s. 791-803
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Journal article (peer-reviewed)abstract
- This paper reports the range and statistical distribution of oxidation rates of atmospheric CH4 in soils found in Northern Europe in an international study, and compares them with published data for various other ecosystems. It reassesses the size, and the uncertainty in, the global terrestrial CH4 sink, and examines the effect of land-use change and other factors on the oxidation rate. Only soils with a very high water table were sources of CH4, all others were sinks. Oxidation rates varied from 1 to nearly 200 µg CH4 m-2 h-1, annual rates for sites measured for =1 y were 0.1-9.1 kg CH4 ha-1 y-1, with a log-normal distribution (log-mean ~ 1.6 kg CH4 ha-1 y-1). Conversion of natural soils to agriculture reduced oxidation rates by two-thirds - closely similar to results reported for other regions. N inputs also decreased oxidation rates. Full recovery of rates after these disturbances takes > 100 y. Soil bulk density, water content and gas diffusivity had major impacts on oxidation rates. Trends were similar to those derived from other published work. Increasing acidity reduced oxidation, partially but not wholly explained by poor diffusion through litter layers which did not themselves contribute to the oxidation. The effect of temperature was small, attributed to substrate limitation and low atmospheric concentration. Analysis of all available data for CH4 oxidation rates in situ showed similar log-normal distributions to those obtained for our results, with generally little difference between different natural ecosystems, or between short-and longer-term studies. The overall global terrestrial sink was estimated at 29 Tg CH4 y-1, close to the current IPCC assessment, but with a much wider uncertainty range (7 to > 100 Tg CH4 y-1). Little or no information is available for many major ecosystems, these should receive high priority in future research.
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| 11. |
- Aidas, Kestutis, et al.
(author)
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The Dalton quantum chemistry program system
- 2014
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In: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Journal article (peer-reviewed)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 12. |
- Bakken, K. S., et al.
(author)
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Higher risk for adverse obstetric outcomes among immigrants of African and Asian Descent: A comparison study at a low-risk maternity hospital in Norway
- 2015
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In: Birth. - : Wiley. - 0730-7659 .- 1523-536X. ; 42:2, s. 132-140
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Journal article (peer-reviewed)abstract
- Background: Immigrants have higher risks for some adverse obstetric outcomes, and 40 percent of women giving birth at the low-risk maternity ward in Baerum Hospital, Norway, are immigrants. This study compared obstetric outcomes between immigrants and ethnic Norwegians giving birth in a low-risk setting. Methods: This was a population-based study linking the Medical Birth Registry of Norway to Statistics Norway. The study included the first registered birth during the study period to immigrant and ethnic Norwegian women at Baerum Hospital from 2006 to 2010. The main outcome measures were onset of labor, operative vaginal delivery, cesarean delivery, episiotomy, postpartum bleeding >500mL, epidural analgesia, labor dystocia, gestational age, meconium-stained liquor, 5-minute Apgar score, birthweight, and transfer to a neonatal intensive care unit. Results: A total of 11,540 women originating from 141 countries were divided into seven groups. Compared with Norwegians, women from East, Southeast, and Central Asia had increased risk for operative vaginal delivery, postpartum bleeding, and low Apgar score. The African women had increased risk for postterm birth, meconium-stained liquor, episiotomy, operative vaginal delivery, emergency cesarean delivery, postpartum bleeding, low Apgar score, and low birthweight. Women from South and Western Asia had increased risk for low birthweight. Conclusion: Obstetric outcomes of immigrants differ significantly from those of Norwegians, even in a low-risk maternity unit. Thus, immigrant women would benefit from more targeted care during pregnancy and childbirth, even in low-risk settings. © 2015 Wiley Periodicals, Inc.
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| 13. |
- Bakken, K. S., et al.
(author)
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Immigrants from conflict-zone countries: an observational comparison study of obstetric outcomes in a low-risk maternity ward in Norway
- 2015
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In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 15
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Journal article (peer-reviewed)abstract
- Background: Immigrants have higher risks for some adverse obstetric outcomes. Furthermore, refugees are reported to be the most vulnerable group. This study compared obstetric outcomes between immigrant women originating from conflict-zone countries and ethnic Norwegians who gave birth in a low-risk setting. Methods: This was a population-based study linking the Medical Birth Registry of Norway to Statistics Norway. The study included the first registered birth during the study period of women from Somalia (n = 278), Iraq (n = 166), Afghanistan (n = 71), and Kosovo (n = 67) and ethnic Norwegians (n = 6826) at Baerum Hospital from 2006-2010. Background characteristics and obstetric outcomes of each immigrant group were compared with ethnic Norwegians with respect to proportions and risks calculated by logistic regression models. Results: In total, 7408 women and their births were analyzed. Women from Somalia were most at risk for adverse obstetric outcomes. Compared with ethnic Norwegians, they had increased odds ratios (OR) for emergency cesarean section (OR 1.81, CI 1.17-2.80), postterm birth (OR 1.93, CI 1.29-2.90), meconium-stained liquor (OR 2.39, CI 1.76-3.25), and having a small-for-gestational-age infant (OR 3.97, CI 2.73-5.77). They had a reduced OR for having epidural analgesia (OR 0.40, CI 0.28-0.56) and a large-for-gestational-age infant (OR 0.32, CI 0.16-0.64). Women from Iraq and Afghanistan had increased risk of having a small-for-gestational-age infant with OR of 2.21 (CI 1.36-3.60) and 2.77 (CI 1.42-5.39), respectively. Iraqi women also had reduced odds ratio of having a large-for-gestational-age infant (OR 0.35, CI 0.15-0.83). Women from Kosovo did not differ from ethnic Norwegians in any of the outcomes we tested. Conclusions: Even in our low-risk maternity ward, women originating from Somalia were at the greatest risk for adverse obstetric outcomes in the compared groups. We could not find the same risk among the other immigrant women, also originating from conflict-zone countries. Several factors may influence these findings, and this study suggests that immigrant women from Somalia need more targeted care during pregnancy and childbirth.
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| 14. |
- Duell, Eric J, et al.
(author)
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Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition
- 2010
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:12, s. 1384-1393
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Journal article (peer-reviewed)abstract
- The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.
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| 15. |
- Kyro, C., et al.
(author)
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ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
- 2013
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In: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 1207-1208
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Journal article (other academic/artistic)abstract
- Background and objectives: Few studies have investigatedthe association between whole-grain intake and colorectal cancer.Whole-grain products are one of the dietary items proneto measurement errors, making the use of objective measures,such as biomarkers, highly relevant. The objective of the studywas to investigate the association between biomarkers ofwhole-grain intake, alkylresorcinols, and colorectal cancer ina nested case-control study within the European ProspectiveInvestigation into Cancer and Nutrition (EPIC). Methods: We included 1372 first incident colorectal cancercases and 1372 individually matched controls and calculatedthe incidence rate ratios (IRR) for overall and sub-sites of colorectalcancer using conditional logistic regression adjusted forpotential confounders.Results: Plasma total alkylresorcinol concentrations werenot associated with risk of overall colorectal cancer, proximalcolon cancer or rectal cancer. However, high plasma total alkylresorcinolconcentrations were statistically significantly associatedwith lower incidence of cancer located in the distal (leftor descending) part of the colon. Adjusted IRR of distal coloncancer for highest versus lowest quartile of plasma alkylresorcinolwas 0.48 (95% confidence interval = 0.28 to 0.83). Furthermore,we observed an inverse association with colon cancerfor the Scandinavian part of the participants. Alkylresorcinolsmay be more appropriate as biomarkers in Middle Europe andScandinavia i.e. in areas where whole grains are regularly consumed.Conclusions: Whole-grain intake, assessed by alkylresorcinols,was associated with a lower incidence of distal coloncancer. Alkylresorcinols seem useful as objective biomarkersof whole-grain intake in populations where whole-grains are astaple part of the diet. Acknowledgements: This work was supportedby World Cancer Research Fund International (WCRF)and WCRF Netherlands (WCRF NL) (2011/436), and NordForsk(Centre of Excellence programme HELGA (070015)).
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| 16. |
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| 17. |
- Kyrø, Cecilie, et al.
(author)
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Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2014
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In: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 111:10, s. 1881-1890
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Journal article (peer-reviewed)abstract
- Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.
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| 18. |
- Kyrø, Cecilie, et al.
(author)
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Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer
- 2014
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 106:1, s. djt352-
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Journal article (peer-reviewed)abstract
- Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
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| 19. |
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| 20. |
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| 21. |
- Martinsson, Svante, 1985, et al.
(author)
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Species delimitation and phylogeny of Doto (Nudibranchia: Dotidae) from the Northeast Atlantic, with a discussion on food specialization
- 2021
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In: Journal of Zoological Systematics and Evolutionary Research. - : Hindawi Limited. - 0947-5745 .- 1439-0469. ; 59:8, s. 1754-1774
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Journal article (peer-reviewed)abstract
- The nudibranch genus Doto is taxonomically problematic in particular, and some species are described on the notion of strict monophagy. Here we perform species delimitation on NE Atlantic species, as well as placing them phylogenetically, using two markers: the mitochondrial COI and the nuclear H3. We also study the morphology of the species including radular ultrastructure and review food specificity. Specimens were first divided into potential species using ABDG on both markers, these groups were used as input species for species delimitation analyses using BPP, and analyses were performed with both markers combined and on H3 only. The analyses delimit 11 and eight species, respectively. With the exception of one species for which only COI was available, the differences are found in D. fragilis, which is split into three groups when COI is included and lumped into one with only H3. Doto hystrix is nested within these groups. We also found that specimens from Sweden seemingly close to D. maculata in external morphology have identical sequences as D. coronata. Analysis of food preferences of the species involved in the study contradicts the notion of strict monophagy within Doto.
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| 22. |
- Michaud, Dominique S., et al.
(author)
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Reproductive Factors and Exogenous Hormone Use in Relation to Risk of Glioma and Meningioma in a Large European Cohort Study
- 2010
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 19:10, s. 2562-2569
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Journal article (peer-reviewed)abstract
- Background: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI). Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46). Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562-9. (C) 2010 AACR.
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| 23. |
- Mittler, Eva, et al.
(author)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Journal article (peer-reviewed)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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| 24. |
- Mittler, Eva, et al.
(author)
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Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
- 2023
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
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Journal article (peer-reviewed)abstract
- Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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| 25. |
- Normann, EK, et al.
(author)
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Treatment of acute neonatal bacterial conjunctivitis: a comparison of fucidic acid to chloramphenicol eye drops
- 2002
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 80:2, s. 183-187
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Journal article (peer-reviewed)abstract
- Purpose: To compare the clinical and bacteriological effects of fucidic acid (Fucithalmic(R): 1.0%) and chloramphenicol (Minims(R): 0.5%) eye drops in neonates with a clinical diagnosis of acute conjunctivitis of suspected bacterial origin. Methods: A total of 456 newborns with gestational age > 32 weeks with acute conjunctivitis of suspected bacterial origin acquired within the first 28 days of life were included in the study. They were randomly assigned to a 7-day treatment with eye drops using either fucidic acid (1.0%) (Fucithalmic(R)) applied or chloramphenicol (0.5%) (Minims(R) Chloramphenicol) applied twice per day six times per day. The subjects were followed up with two visits (on days 1 and 8) and by telephone 2 weeks after the end of treatment. Results: Eighty-nine per cent of the neonates treated with Fucithalmic(R) were cured, compared to 87.9% of those treated with Minims(R) Chloramphenicol (n.s). The drug was used as instructed in 90.7% of patients treated with Fucithalmic(R) and in 78.0% of those treated with Minims(R) Chloramphenicol (P < 0.001). Conclusion: Treating neonatal conjunctivitis with fucidic acid is easier than with chloramphenicol and is equally effective.
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| 26. |
- Nygren, Arne, 1971, et al.
(author)
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A mega-cryptic species complex hidden among one of the most common annelids in the North East Atlantic
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6
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Journal article (peer-reviewed)abstract
- We investigate mitochondrial (COI, 16S rDNA) and nuclear (ITS2, 28S rDNA) genetic structure of North East Atlantic lineages of Terebellides, a genus of sedentary annelids mainly inhabiting continental shelf and slope sediments. We demonstrate the presence of more than 25 species of which only seven are formally described. Species boundaries are determined with molecular data using a broad range of analytical methods. Many of the new species are common and wide spread, and the majority of the species are found in sympatry with several other species in the complex. Being one of the most regularly encountered annelid taxa in the North East Atlantic, it is more likely to find an undescribed species of Terebellides than a described one.
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| 27. |
- Schander, C, 1960, et al.
(author)
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The fauna of hydrothermal vents on the Mohn Ridge (North Atlantic)
- 2010
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In: Marine Biology Research. - 1745-1000. ; 6:2, s. 155-171
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Journal article (peer-reviewed)abstract
- The macrofauna of the newly discovered hydrothermal vent field on the Mohn Ridge at 71 degrees N was investigated. Samples were collected during the cruise BIODEEP 2006 using the ROV 'Bathysaurus'. A total of 180 species-level taxa were identified. The region contains very few vent-endemic species, but some species of Porifera, Crustacea and Mollusca may be vent-associated. Dense aggregations of motile non-vent species such as Heliometra glacialis and Gorgonocephalus eucnemis surrounded the vent area, but the area in general only held small numbers of sedentary animals. Calcareous sponges comprised an unusually high portion of the sponge species found and they constitute one of the first pioneers among the sessile invertebrates settling on these vents. Possible explanations for the structure of the fauna in the region are discussed.
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| 28. |
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