| 1. |
- Bunce, R. G. H., et al.
(författare)
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A standardized procedure for surveillance and monitoring European habitats and provision of spatial data
- 2008
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Ingår i: Landscape Ecology. - : Springer Science and Business Media LLC. - 0921-2973 .- 1572-9761. ; 23, s. 11-25
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Tidskriftsartikel (refereegranskat)abstract
- Both science and policy require a practical, transmissible, and reproducible procedure for surveillance and monitoring of European habitats, which can produce statistics integrated at the landscape level. Over the last 30 years, landscape ecology has developed rapidly, and many studies now require spatial data on habitats. Without rigorous rules, changes from baseline records cannot be separated reliably from background noise. A procedure is described that satisfies these requirements and can provide consistent data for Europe, to support a range of policy initiatives and scientific projects. The methodology is based on classical plant life forms, used in biogeography since the nineteenth century, and on their statistical correlation with the primary environmental gradient. Further categories can therefore be identified for other continents to assist large scale comparisons and modelling. The model has been validated statistically and the recording procedure tested in the field throughout Europe. A total of 130 General Habitat Categories (GHCs) is defined. These are enhanced by recording environmental, site and management qualifiers to enable flexible database interrogation. The same categories are applied to areal, linear and point features to assist recording and subsequent interpretation at the landscape level. The distribution and change of landscape ecological parameters, such as connectivity and fragmentation, can then be derived and their significance interpreted.
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| 2. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 4. |
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| 5. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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| 6. |
- Karawita, Anjana C., et al.
(författare)
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The swan genome and transcriptome, it is not all black and white
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information.ResultsHere, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan.ConclusionTogether, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.
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| 7. |
- Laumer, W., et al.
(författare)
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A novel approach for the homogenization of cellulose to use micro-amounts for stable isotope analyses
- 2009
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 23:13, s. 1934-1940
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Tidskriftsartikel (refereegranskat)abstract
- Climate reconstructions using stable isotopes from tree-rings are steadily increasing. The investigations concentrate mostly on cellulose due to its high stability. In recent years the available amount of cellulose has steadily decreased, mainly because micro-structures of plant material have had to be analyzed. Today, the amounts of cellulose being studied are frequently in the milligram and often in the microgram range. Consequently, homogeneity problems with regard to the stable isotopes of carbon and oxygen from cellulose have occurred and these have called for new methods in the preparation of cellulose for reliable isotope analyses. Three different methods were tested for preparing isotopically homogenous cellulose, namely mechanical grinding, freezing by liquid nitrogen with subsequent milling and ultrasonic breaking of cellulose fibres. The best precision of isotope data was achieved by freeze-milling and ultrasonic breaking. However, equipment for freeze-milling is expensive and the procedure is labour-intensive. Mechanical grinding resulted in a rather high loss of material and it is also labour-intensive. The use of ultrasound for breaking cellulose fibres proved to be the best method in terms of rapidity of sample throughput, avoidance of sample loss, precision of isotope results, ease of handling, and cost.
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| 8. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 9. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 10. |
- Adam, Birgit, et al.
(författare)
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N2-fixation, ammonium release and N-transfer to the microbial and classical food web within a plankton community
- 2016
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 10:2, s. 450-459
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the role of N2-fixation by the colony-forming cyanobacterium, Aphanizomenon spp., for the plankton community and N-budget of the N-limited Baltic Sea during summer by using stable isotope tracers combined with novel secondary ion mass spectrometry, conventional mass spectrometry and nutrient analysis. When incubated with 15N2, Aphanizomenon spp. showed a strong 15N-enrichment implying substantial 15N2-fixation. Intriguingly, Aphanizomenon did not assimilate tracers of 15NH4+ from the surrounding water. These findings are in line with model calculations that confirmed a negligible N-source by diffusion-limited NH4+ fluxes to Aphanizomenon colonies at low bulk concentrations (<250 nm) as compared with N2-fixation within colonies. No N2-fixation was detected in autotrophic microorganisms <5 mum, which relied on NH4+ uptake from the surrounding water. Aphanizomenon released about 50% of its newly fixed N2 as NH4+. However, NH4+ did not accumulate in the water but was transferred to heterotrophic and autotrophic microorganisms as well as to diatoms (Chaetoceros sp.) and copepods with a turnover time of ~5 h. We provide direct quantitative evidence that colony-forming Aphanizomenon releases about half of its recently fixed N2 as NH4+, which is transferred to the prokaryotic and eukaryotic plankton forming the basis of the food web in the plankton community. Transfer of newly fixed nitrogen to diatoms and copepods furthermore implies a fast export to shallow sediments via fast-sinking fecal pellets and aggregates. Hence, N2-fixing colony-forming cyanobacteria can have profound impact on ecosystem productivity and biogeochemical processes at shorter time scales (hours to days) than previously thought.
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| 11. |
- Alexiou, Eirini, et al.
(författare)
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Sustainability of a person-centered ward atmosphere and possibility to provide person-centered forensic psychiatric care after facility relocation
- 2018
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Ingår i: Journal of Forensic and Legal Medicine. - : Elsevier BV. - 1752-928X. ; 56, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This longitudinal study aims to assess the sustainability of staff perceptions of ward atmosphere and their possibility to provide person-centered forensic psychiatric care after relocation to new hospitals that aimed to provide supportive work conditions for the staff to be able to perform care of high quality. Methods: In this study we only present the result for the repeated measures, that is, only the individuals that performed both the questionnaires at baseline and at the three follow-ups. Data were collected prospectively between 2010 and 2016; before (baseline) and after relocation of the forensic psychiatric clinics to new buildings, i.e., after six months (follow-up 1), after one year (follow-up 2) and after two years (follow-up 3), respectively. Data were obtained by employing structured validated questionnaires. Results: The main findings of this study display an improvement in the staff assessment of a person-centered atmosphere from baseline to follow-up 3 in the domains of safety, everydayness and community where safety was evaluated the highest. No sustainable significant changes were found concerning staff's assessment of the support for them to provide person-centered care. Conclusion: The findings show sustainability of person-centered ward atmosphere in forensic psychiatric care according to staff's assessment after relocation from traditional health care facilities to evidence-based designed premises. In this study the increased staff perception of the possibility to provide person-centered care in the new facilities could not be revealed as sustainability over the two years of follow-up.
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| 12. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 13. |
- Amirian, E. Susan, et al.
(författare)
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The Glioma International Case-Control Study : A Report From the Genetic Epidemiology of Glioma International Consortium
- 2016
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 183:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.
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| 14. |
- Arana, Alejandro, et al.
(författare)
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Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus : Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE)
- 2021
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Ingår i: Clinical Epidemiology. - : Dove Medical Press. - 1179-1349. ; 13, s. 1141-1153
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evidence is insufficient to infer whether topical calcineurin inhibitors (TCIs; tacrolimus and pimecrolimus) cause malignancy. The study objective was to estimate the long-term risk of skin cancer and lymphoma associated with topical TCI use in adults and children, separately.Patients and Methods: A cohort study in Denmark, Sweden, UK, and the Netherlands was conducted. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for nonmelanoma skin cancer (NMSC), melanoma, cutaneous T-cell lymphoma (CTCL), non-Hodgkin lymphoma (NHL) excluding CTCL, and Hodgkin lymphoma (HL) in new users of TCIs versus users of moderate/high-potency topical corticosteroids.Results: The study included 126,908/61,841 adults and 32,605/27,961 children initiating treatment with tacrolimus/pimecrolimus, respectively. Follow-up was ≥10 years for 19% of adults and 32% of children. Incidence rate ratios and (95% confidence intervals) for tacrolimus versus corticosteroid users in adults were <1 for melanoma, non-Hodgkin lymphoma, and Hodgkin lymphoma; and 1.80 (1.25-2.58) for cutaneous T-cell lymphoma. For pimecrolimus, IRRs in adults were <1 for non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and Hodgkin's lymphoma; and 1.21 (1.03-1.41) for melanoma; and 1.28 (1.20-1.35) for nonmelanoma skin cancer. In children, results were inconclusive due to few events. In adults, incidence rate ratios ≥5 years after first topical calcineurin inhibitor exposure were not higher than in overall analyses.Conclusion: Overall, we found little evidence associating use of topical calcineurin inhibitors with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. Even if causal, the public health impact of these excess risks would be low and confined to the first years of exposure.
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| 15. |
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| 16. |
- Auffret, Alistair G., et al.
(författare)
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HistMapR : Rapid digitization of historical land-use maps in R
- 2017
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 8:11, s. 1453-1457
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Tidskriftsartikel (refereegranskat)abstract
- Habitat destruction and degradation represent serious threats to biodiversity, and quantification of land-use change over time is important for understanding the consequences of these changes to organisms and ecosystem service provision. Comparing land use between maps from different time periods allows estimation of the magnitude of habitat change in an area. However, digitizing historical maps manually is time-consuming and analyses of change are usually carried out at small spatial extents or at low resolutions. HistMapR contains a number of functions that can be used to semi-automatically digitize historical land use according to a map's colours, as defined by the RGB bands of the raster image. We test the method on different historical land-use map series and compare results to manual digitizations. Digitization is fast, and agreement with manually digitized maps of around 80-90% meets common targets for image classification. We hope that the ability to quickly classify large areas of historical land use will promote the inclusion of land-use change into analyses of biodiversity, species distributions and ecosystem services.
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| 17. |
- Barman, Malin, 1983, et al.
(författare)
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Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery
- 2020
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 123:2, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- The first positive genome-wide association study on gestational length and preterm delivery showed associations with a gene involved in the selenium metabolism. In this study we examine the associations between maternal intake of selenium and selenium status with gestational length and preterm delivery in 72,025 women with singleton live births from the population based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitativ food-frequency questionnaire answered in pregnancy week 22 was used to estimate selenium intake during the first half of pregnancy. Associations were analysed with adjusted linear and cox regressions. Selenium status was assessed in whole blood collected in gestational week 17 (n=2,637). Median dietary selenium intake was 53 (IQR: 44-62) μg/day, supplements provided additionally 50 (30-75) μg/day for supplement-users (n=23,409). Maternal dietary selenium intake was significantly associated with prolonged gestational length (β per SD=0.25, 95% CI=0.07-0.43) and decreased risk for preterm delivery (n=3,618, HR per SD=0.92, 95% CI=0.87-0.98). Neither selenium intake from supplements nor maternal blood selenium status was associated with gestational length or preterm delivery. Hence, this study showed that maternal dietary selenium intake, but not intake of selenium containing supplements, during the first half of pregnancy was significantly associated with decreased risk for preterm delivery. Further investigations, preferably in the form of a large RCT, are needed to elucidate the impact of selenium on pregnancy duration.
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| 18. |
- Bastholt, Lars, et al.
(författare)
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Phase I/II clinical and pharmacokinetic study evaluating a fully human monoclonal antibody against EGFr (HuMax-EGFr) in patients with advanced squamous cell carcinoma of the head and neck
- 2007
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 85:1, s. 24-28
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess safety, tolerability, pharmacokinetics and clinical activity of HuMax-EGFr in patients with SCCHN. Patients and methods: Twenty-eight patients with SCCHN were enrolled. The study comprised a single-dose escalation part for assessment of safety issues followed by a repeat dose extension including 4 weekly infusions at the same doses. Efficacy and metabolic response were evaluated according to RECIST by CT and FDG-PET. Results: Most frequently reported adverse event was rash. All but one event were CTC grade 1 or 2 and a dose-dependent relationship was indicated. Duration of skin reactions varied from few days to 2 months. No DLTs were observed and MTD was not reached. In the two highest dose groups, 7 of 11 patients obtained a PR or SD and 9 patients obtained metabolic PR or SD. Conclusions: HuMax-EGFr can be safety administered in doses up to 8 mg/kg, and preliminary data on tumour response are encouraging. (c) 2007 Elsevier Ireland Ltd.
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| 19. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 20. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 21. |
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| 22. |
- Erhardt, Tobias, et al.
(författare)
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High-resolution aerosol concentration data from the Greenland NorthGRIP and NEEM deep ice cores
- 2022
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:3, s. 1215-1231
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Tidskriftsartikel (refereegranskat)abstract
- Records of chemical impurities from ice cores enable us to reconstruct the past deposition of aerosols onto polar ice sheets and alpine glaciers. Through this they allow us to gain insight into changes of the source, transport and deposition processes that ultimately determine the deposition flux at the coring location. However, the low concentrations of the aerosol species in the ice and the resulting high risk of contamination pose a formidable analytical challenge, especially if long, continuous and highly resolved records are needed. Continuous flow analysis, CFA, the continuous melting, decontamination and analysis of ice-core samples has mostly overcome this issue and has quickly become the de facto standard to obtain high-resolution aerosol records from ice cores after its inception at the University of Bern in the mid-1990s.Here, we present continuous records of calcium (Ca2+), sodium (Na+), ammonium (NH+4), nitrate (NO-3) and electrolytic conductivity at 1 mm depth resolution from the NGRIP (North Greenland Ice Core Project) and NEEM (North Greenland Eemian Ice Drilling) ice cores produced by the Bern Continuous Flow Analysis group in the years 2000 to 2011 (Erhardt et al., 2021). Both of the records were previously used in a number of studies but were never published in full 1 mm resolution. Alongside the 1 mm datasets we provide decadal averages, a detailed description of the methods, relevant references, an assessment of the quality of the data and its usable resolution. Along the way we will also give some historical context on the development of the Bern CFA system.
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| 23. |
- Ericsson, Henrik, et al.
(författare)
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Molecular grouping of Listeria monocytogenes based on the sequence of the inlB gene
- 2000
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 49:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- The major part of the gene inlB was sequenced in 24 strains of Listeria monocytogenes belonging to serovars 1/2a, 1/2b, 1/2c, 3b and 4b. A phylogenetic analysis based on the inlB nucleotide sequences showed that strains of serovars 1/2a and 1/2c were closely related, as well as those of serovars 1/2b and 3b. Strains sharing serovar 4b could be divided into two distinct groups. There were differences in amino-acid sequence between all serovars except between serovars 1/2b and 3b. Differences in amino-acid sequence were also seen within each of the serovars 1/2a and 4b. The data presented indicate that the inlB gene may be useful for typing purposes as an alternative or complement to serotyping.
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| 24. |
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| 25. |
- Gudmundsdottir, Valborg, et al.
(författare)
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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study
- 2020
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.Conclusions: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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| 26. |
- Gutema, G., et al.
(författare)
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Multiple challenges of antibiotic use in a large hospital in Ethiopia - a ward-specific study showing high rates of hospital-acquired infections and ineffective prophylaxis
- 2018
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: This project aims to study the use of antibiotics in three clinical wards in the largest tertiary teaching hospital in Ethiopia for a period of 1 year. The specific aims were to assess the prevalence of patients on antibiotics, quantify the antibiotic consumption and identify the main indications of use. Method: The material was all the medical charts (n = 2231) retrieved from three clinical wards (internal medicine, gynecology/obstetrics and surgery) in Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa between September 2013 and September 2014. Data collection was performed manually by four pharmacists. Results: Each medical chart represented one patient. About 60% of the patients were admitted to internal medicine, 20% to each of the other two wards. The number of bed days (BD) was on average 16.5. Antibiotics for systemic use were prescribed to 73.7% of the patients (on average: 2.1 antibiotics/patient) of whom 86.6% got a third or fourth generation cephalosporin (mainly ceftriaxone). The average consumption of antibiotics was 81.6 DDD/100BD, varying from 91.8 in internal medicine and 71.6 in surgery to 47.6 in gynecology/obstetrics. The five most frequently occurring infections were pneumonia (26.6%), surgical site infections (21.5%), neutropenic fever (6.9%), sepsis (6.4%) and urinary tract infections (4.7%). About one fourth of the prescriptions were for prophylactic purposes. Hospital acquired infections occurred in 23.5% of the patients (353 cases of surgical site infection). The prescribing was based on empirical treatment and sensitivity testing was reported in only 3.8% of the cases. Conclusions: In the present study from three wards in the largest tertiary teaching hospital in Ethiopia, three out of four patients were prescribed antibiotics, primarily empirically. The mean antibiotic consumption was 81.6 DDD/100BD. Surgical site infections constituted a large burden of the infections treated in the hospital, despite extensive prescribing of prophylaxis. The findings show the need to implement antibiotic stewardship programs in Ethiopian hospitals with focus on rational prescribing, increased sensitivity testing and better procedures to prevent hospital acquired infections.
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| 27. |
- Haggblom-Kronlof, G, et al.
(författare)
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Editorial
- 2017
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Ingår i: Scandinavian journal of occupational therapy. - : Informa UK Limited. - 1651-2014 .- 1103-8128. ; 24:4, s. 233-234
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Hefzi, Hooman, et al.
(författare)
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Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. In contrast to long-standing assumptions about the role of aerobic glycolysis, Warburg-null cells maintain wildtype growth rate while producing negligible lactate. Further characterization of Warburg-null CHO cells showed a compensatory increase in oxygen consumption, a near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. These cells remained amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titers and maintaining product glycosylation. Thus, the ability to eliminate the Warburg effect is an important development for biotherapeutic production and provides a tool for investigating a near-universal metabolic phenomenon.
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| 29. |
- Hultman, Christina M, et al.
(författare)
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Ethical Issues in Cancer Register Follow-Up of Hormone Treatment in Adolescence
- 2009
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Ingår i: Public Health Ethics. - : Oxford University Press (OUP). - 1754-9973 .- 1754-9981. ; 2:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Since the 1970s, estrogen have sometimes been used in adolescent girls to reduce very tall adult expected height.Worries about long-term effects have led to a proposal to link treatment data with cancer registers. How shouldone deal with informed consent for such a study?We designed a qualitative study with semi-structured telephoneinterviews. From 1200 women who were to be followed-up in cancer registers, we randomly selected 22 women.Major themes were a wish to be involved and a positive attitude to the proposed register research. The womendid not express worry after reading the study protocol, but did convey considerable frustration that this researchhad not been initiated earlier. Active consent was not seen as crucial. We found strong interest in a high participationrate and a concern over missing data. The selection of information and consent or the decision to goahead without consent in register follow-up is a delicate balancing act. Study participants wish to be contacted,but acknowledge the primary goal of answering important questions. Our study provides support for safeguardingprivacy in epidemiological linkage studies and in follow-up of medical treatment without losing the scientificvalue by requesting for informed consent.
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| 30. |
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| 31. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 32. |
- Klawonn, Isabell, et al.
(författare)
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Simple approach for the preparation of N-15-15(2)-enriched water for nitrogen fixation assessments: evaluation, application and recommendations
- 2015
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings revealed that the commonly used N-15(2) tracer assay for the determination of dinitrogen (N-2) fixation can underestimate the activity of aquatic N-2-fixing organisms. Therefore, a modification to the method using pre-prepared N-15-15(2)-enriched water was proposed. Here, we present a rigorous assessment and outline a simple procedure for the preparation of N-15-15(2)-enriched water. We recommend to fill sterile-filtered water into serum bottles and to add N-15-15(2) gas to the water in amounts exceeding the standard N-2 solubility, followed by vigorous agitation (vortex mixing >= 5 min). Optionally, water can be degassed at low-pressure (>= 950 mbar) for 10 mm prior to the N-15-15(2) gas addition to indirectly enhance the N-15-15(2) concentration. This preparation of N-15-15(2)-enriched water can be done within 1 h using standard laboratory equipment. The final N-15-atom% excess was 5% after replacing 2-5% of the incubation volume with N-15-15(2)-enriched water. Notably, the addition of N-15-15(2)-enriched water can alter levels of trace elements in the incubation water due to the contact of N-15-15(2)-enriched water with glass, plastic and rubber ware. In our tests, levels of trace elements (Fe, P, Mn, Mo, Cu, Zn) increased by up to 0.1 nmol L-1 in the final incubation volume, which may bias rate measurements in regions where N-2 fixation is limited by trace elements. For these regions, we tested an alternative way to enrich water with N-15-15(2). The N-15-15(2) was injected as a bubble directly to the incubation water, followed by gentle shaking. Immediately thereafter, the bubble was replaced with water to stop the N-15-15(2) equilibration. This approach achieved a N-15-atom% excess of 6.6 +/- 1.7% when adding 2 mL N-15-15(2) per liter of incubation water. The herein presented methodological tests offer guidelines for the N-15(2) tracer assay and thus, are crucial to circumvent methodological draw-backs for future N-2 fixation assessments.
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| 33. |
- Kliest, Tessa, et al.
(författare)
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Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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| 34. |
- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 35. |
- Liñán, I. Dorado, et al.
(författare)
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Estimating 750 years of temperature variations and uncertainties in the Pyrenees by tree ring reconstructions and climate simulations
- 2012
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 8:3, s. 919-933
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Tidskriftsartikel (refereegranskat)abstract
- Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.
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| 36. |
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| 37. |
- Marklund, Matti, et al.
(författare)
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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality : An Individual-Level Pooled Analysis of 30 Cohort Studies
- 2019
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 139:21, s. 2422-2436
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Tidskriftsartikel (refereegranskat)abstract
- Background:Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.Methods:We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).Results:In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.Conclusions:In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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| 38. |
- McCarthy, Bridget J, et al.
(författare)
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Risk factors for oligodendroglial tumors : A pooled international study
- 2011
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Ingår i: Neuro-Oncology. - Charlottesville, VA : Carden Jennings Pub.. - 1522-8517 .- 1523-5866. ; 13:2, s. 242-250
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Tidskriftsartikel (refereegranskat)abstract
- Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
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| 39. |
- Niels J., Schoffelen, et al.
(författare)
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Phosphate availability affects fixed nitrogen transfer from diazotrophs to their epibionts
- 2019
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 13, s. 2701-2713
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Tidskriftsartikel (refereegranskat)abstract
- Dinitrogen (N2) fixation is a major source of external nitrogen (N) to aquatic ecosystems and therefore exerts control over productivity. Studies have shown that N2 -fixers release freshly fixed N into the environment, but the causes for this N release are largely unclear. Here, we show that the availability of phosphate can directly affect the transfer of freshly fixed N to epibionts in filamentous, diazotrophic cyanobacteria. Stable-isotope incubations coupled to single-cell analyses showed that <1% and ~15% of freshly fixed N was transferred to epibionts of Aphanizomenon and Nodularia, respectively, at phosphate scarcity during a summer bloom in the Baltic Sea. When phosphate was added, the transfer of freshly fixed N to epibionts dropped to about half for Nodularia, whereas the release from Aphanizomenon increased slightly. At the same time, the growth rate of Nodularia roughly doubled, indicating that less freshly fixed N was released and was used for biomass production instead. Phosphate scarcity and the resulting release of freshly fixed N could explain the heavy colonization of Nodularia filaments by microorganisms during summer blooms. As such, the availability of phosphate may directly affect the partitioning of fixed N2 in colonies of diazotrophic cyanobacteria and may impact the interactions with their microbiome.
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| 40. |
- Palmer, Jonathan G., et al.
(författare)
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Changes in El Niño – Southern Oscillation (ENSO) conditions during the Greenland Stadial 1 (GS-1) chronozone revealed by New Zealand tree-rings
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 153, s. 139-155
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Tidskriftsartikel (refereegranskat)abstract
- The warming trend at the end of the last glacial was disrupted by rapid cooling clearly identified in Greenland (Greenland Stadial 1 or GS-1) and Europe (Younger Dryas Stadial or YD). This reversal to glacial-like conditions is one of the best known examples of abrupt change but the exact timing and global spatial extent remain uncertain. Whilst the wider Atlantic region has a network of high-resolution proxy records spanning GS-1, the Pacific Ocean suffers from a scarcity of sub-decadally resolved sequences. Here we report the results from an investigation into a tree-ring chronology from northern New Zealand aimed at addressing the paucity of data. The conifer tree species kauri (Agathis australis) is known from contemporary studies to be sensitive to regional climate changes. An analysis of a ‘historic’ 452-year kauri chronology confirms a tropical-Pacific teleconnection via the El Niño – Southern Oscillation (ENSO). We then focus our study on a 1010-year sub-fossil kauri chronology that has been precisely dated by comprehensive radiocarbon dating and contains a striking ring-width downturn between ∼12,500 and 12,380 cal BP within GS-1. Wavelet analysis shows a marked increase in ENSO-like periodicities occurring after the downturn event. Comparison to low- and mid-latitude Pacific records suggests a coherency with ENSO and Southern Hemisphere atmospheric circulation change during this period. The driver(s) for this climate event remain unclear but may be related to solar changes that subsequently led to establishment and/or increased expression of ENSO across the mid-latitudes of the Pacific, seemingly independent of the Atlantic and polar regions.
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| 41. |
- Parker, C., et al.
(författare)
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Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:3, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- Background Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. Methods In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. Results At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. Conclusions In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)
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| 42. |
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| 43. |
- Pritzkow, C., et al.
(författare)
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Relationship between wood anatomy, tree-ring widths and wood density of Pinus sylvestris L. and climate at high latitudes in northern Sweden
- 2014
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Ingår i: Dendrochronologia. - : Elsevier BV. - 1125-7865 .- 1612-0051. ; 32:4, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- In this study, wood anatomy, tree-ring width and wood density of Pinus sylvestris at the northern timberline in Fennoscandia were used to identify relationships among the parameters and to screen them for their climatic signals. Furthermore we investigated the influence of the juvenile wood section for all parameters developed. The measurements of wood anatomy were conducted with confocal laser scanning microscopy (CLSM) while the density profiles were produced using an Itrax MultiScanner. We developed chronologies of ring width, wood density and anatomy for a period between 1940 and 2010. Correlations between wood density and wood anatomy were strong in the latewood part. For some wood anatomy and density chronologies youth trends were found in the juvenile part. Wood density decreased from the pith up to the 9th ring and stabilized afterwards, while cell lumen diameter and lumen area increased simultaneously up to the 15th ring. All chronologies contained strong summer temperature signals. The wood anatomical variables provided additional information about seasonal precipitation which could not be found in wood density and tree-ring widths. Our study confirmed previous results stating that the parameter maximum density contains the strongest climate signal, that is, summer temperatures at the northern timberline. Nevertheless, the intra-annual data on tracheid dimensions showed good potential to supply seasonal climatic information and improve our understanding of climatic effects on tree growth and wood formation.
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| 44. |
- Raatikainen, Kaisa J., et al.
(författare)
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Pathways towards a sustainable future envisioned by early-career conservation researchers
- 2021
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Ingår i: CONSERVATION SCIENCE AND PRACTICE. - : John Wiley & Sons. - 2578-4854. ; 3:9
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Tidskriftsartikel (refereegranskat)abstract
- Scientists have warned decision-makers about the severe consequences of the global environmental crisis since the 1970s. Yet ecological degradation continues and little has been done to address climate change. We investigated early-career conservation researchers' (ECR) perspectives on, and prioritization of, actions furthering sustainability. We conducted a survey (n = 67) and an interactive workshop (n = 35) for ECR attendees of the 5th European Congress of Conservation Biology (2018). Building on these data and discussions, we identified ongoing and forthcoming advances in conservation science. These include increased transdisciplinarity, science communication, advocacy in conservation, and adoption of a transformation-oriented social-ecological systems approach to research. The respondents and participants had diverse perspectives on how to achieve sustainability. Reformist actions were emphasized as paving the way for more radical changes in the economic system and societal values linked to the environment and inequality. Our findings suggest that achieving sustainability requires a strategy that (1) incorporates the multiplicity of people's views, (2) places a greater value on nature, and (3) encourages systemic transformation across political, social, educational, and economic realms on multiple levels. We introduce a framework for ECRs to inspire their research and practice within conservation science to achieve real change in protecting biological diversity.
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| 45. |
- Schollaen, K., et al.
(författare)
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ENSO flavors in a tree-ring delta O-18 record of Tectona grandis from Indonesia
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:10, s. 1325-1333
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Tidskriftsartikel (refereegranskat)abstract
- Indonesia's climate is dominated by the equatorial monsoon system, and has been linked to El Nino-Southern Oscillation (ENSO) events that often result in extensive droughts and floods over the Indonesian archipelago. In this study we investigate ENSO-related signals in a tree-ring delta O-18 record (1900-2007) of Javanese teak. Our results reveal a clear influence of Warm Pool (central Pacific) El Nino events on Javanese tree-ring delta O-18, and no clear signal of Cold Tongue (eastern Pacific) El Nino events. These results are consistent with the distinct impacts of the two ENSO flavors on Javanese precipitation, and illustrate the importance of considering ENSO flavors when interpreting palaeoclimate proxy records in the tropics, as well as the potential of palaeoclimate proxy records from appropriately selected tropical regions for reconstructing past variability of. ENSO flavors.
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| 46. |
- Solé Navais, Pol, et al.
(författare)
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Maternal dietary selenium intake during pregnancy is associated with higher birth weight and lower risk of small for gestational age births in the norwegian mother, father and child cohort study
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 13:1, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Selenium is an essential trace element involved in the body’s redox reactions. Low selenium intake during pregnancy has been associated with low birth weight and an increased risk of children being born small for gestational age (SGA). Based on data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN), we studied the association of maternal selenium intake from diet and supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with birth weight and SGA status, according to population-based, ultrasound-based and customized growth standards. An increase of one standard deviation of maternal dietary selenium intake was associated with increased birth weight z-scores (ß = 0.027, 95% CI: 0.007, 0.041) and lower SGA risk (OR = 0.91, 95% CI 0.86, 0.97) after adjusting for confounders. Maternal organic and inorganic selenium intake from supplements as well as whole blood selenium concentration were not associated with birth weight or SGA. Our results suggest that a maternal diet rich in selenium during pregnancy may be beneficial for foetal growth. However, the effect estimates were small and further studies are needed to elucidate the potential impact of selenium on foetal growth.
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| 47. |
- Tekpli, Xavier, et al.
(författare)
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An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast cancer gene expression datasets, we invariably identify three clusters of patients with gradual levels of immune infiltration. The intermediate immune infiltration cluster (Cluster B) is associated with a worse prognosis independently of known clinicopathological features. Furthermore, immune clusters are associated with response to neoadjuvant chemotherapy. In silico dissection of the immune contexture of the clusters identified Cluster A as immune cold, Cluster C as immune hot while Cluster B has a pro-tumorigenic immune infiltration. Through phenotypical analysis, we find epithelial mesenchymal transition and proliferation associated with the immune clusters and mutually exclusive in breast cancers. Here, we describe immune clusters which improve the prognostic accuracy of immune contexture in breast cancer. Our discovery of a novel independent prognostic factor in breast cancer highlights a correlation between tumor phenotype and immune contexture.
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| 48. |
- Thomas, Wieloch, et al.
(författare)
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A novel device for batch-wise isolation of a-cellulose from small-amount wholewood samples
- 2011
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Ingår i: Dendrochronologia. - : Elsevier BV. - 1125-7865 .- 1612-0051. ; 29:2, s. 115-117
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Tidskriftsartikel (refereegranskat)abstract
- A novel device for the chemical isolation of α-cellulose from wholewood material of tree rings was designed by the Potsdam Dendro Laboratory. It allows the simultaneous treatment of up to several hundred micro samples. Key features are the batch-wise exchange of the chemical solutions, the reusability of all major parts and the easy and unambiguous labelling of each individual sample. Compared to classical methods labour intensity and running costs are significantly reduced.
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| 49. |
- Unnerstad, Helle, et al.
(författare)
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Pyrosequencing as a method for grouping of Listeria monocytogenes strains on the basis of single-nucleotide polymorphisms in the inlB gene
- 2001
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Ingår i: Applied and Environmental Microbiology. - Washington, USA : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 67:11, s. 5339-5342
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Tidskriftsartikel (refereegranskat)abstract
- By using pyrosequencing (i.e., sequencing by synthesis) 106 strains of different serovars of Listeria monocytogenes were rapidly grouped into four categories based on nucleotide variations at positions 1575 and 1578 of the inlB gene. Strains of serovars 1/2a and 1/2c constituted one group, and strains of serovars 1/2b and 3b constituted another group, whereas serovar 4b strains were separated into two groups.
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| 50. |
- Vallejo-Vaz, Antonio J, et al.
(författare)
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Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study FromDA VINCI.
- 2022
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Ingår i: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206.
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Tidskriftsartikel (refereegranskat)abstract
- Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (<70 vs.<55mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated.DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy(LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C≥70mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of<70 or<55mg/dl (LDL-C of 69 or 54mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs andARRs) were simulated.Of the 2039 patients, 61% did not achieve LDL-C<70mg/dl. For patients with LDL-C≥70mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively.In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10years versusthe ACC/AHA approach.
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