| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Meyer, H., et al.
(author)
-
Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
-
In: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
-
Journal article (peer-reviewed)abstract
- Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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| 3. |
- Meyer, H., et al.
(author)
-
Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
-
In: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
-
Journal article (peer-reviewed)abstract
- Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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| 4. |
- Labit, B., et al.
(author)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
-
In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
-
Journal article (peer-reviewed)abstract
- © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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| 5. |
- Coda, S., et al.
(author)
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Physics research on the TCV tokamak facility: From conventional to alternative scenarios and beyond
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Journal article (peer-reviewed)abstract
- The research program of the TCV tokamak ranges from conventional to advanced-tokamak scenarios and alternative divertor configurations, to exploratory plasmas driven by theoretical insight, exploiting the device's unique shaping capabilities. Disruption avoidance by real-time locked mode prevention or unlocking with electron-cyclotron resonance heating (ECRH) was thoroughly documented, using magnetic and radiation triggers. Runaway generation with high-Z noble-gas injection and runaway dissipation by subsequent Ne or Ar injection were studied for model validation. The new 1 MW neutral beam injector has expanded the parameter range, now encompassing ELMy H-modes in an ITER-like shape and nearly non-inductive H-mode discharges sustained by electron cyclotron and neutral beam current drive. In the H-mode, the pedestal pressure increases modestly with nitrogen seeding while fueling moves the density pedestal outwards, but the plasma stored energy is largely uncorrelated to either seeding or fueling. High fueling at high triangularity is key to accessing the attractive small edge-localized mode (type-II) regime. Turbulence is reduced in the core at negative triangularity, consistent with increased confinement and in accord with global gyrokinetic simulations. The geodesic acoustic mode, possibly coupled with avalanche events, has been linked with particle flow to the wall in diverted plasmas. Detachment, scrape-off layer transport, and turbulence were studied in L- and H-modes in both standard and alternative configurations (snowflake, super-X, and beyond). The detachment process is caused by power 'starvation' reducing the ionization source, with volume recombination playing only a minor role. Partial detachment in the H-mode is obtained with impurity seeding and has shown little dependence on flux expansion in standard single-null geometry. In the attached L-mode phase, increasing the outer connection length reduces the in-out heat-flow asymmetry. A doublet plasma, featuring an internal X-point, was achieved successfully, and a transport barrier was observed in the mantle just outside the internal separatrix. In the near future variable-configuration baffles and possibly divertor pumping will be introduced to investigate the effect of divertor closure on exhaust and performance, and 3.5 MW ECRH and 1 MW neutral beam injection heating will be added.
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| 6. |
- Coda, S., et al.
(author)
-
Overview of the TCV tokamak program : Scientific progress and facility upgrades
- 2017
-
In: Nuclear Fusion. - : Institute of Physics Publishing. - 0029-5515 .- 1741-4326. ; 57:10
-
Journal article (peer-reviewed)abstract
- The TCV tokamak is augmenting its unique historical capabilities (strong shaping, strong electron heating) with ion heating, additional electron heating compatible with high densities, and variable divertor geometry, in a multifaceted upgrade program designed to broaden its operational range without sacrificing its fundamental flexibility. The TCV program is rooted in a three-pronged approach aimed at ITER support, explorations towards DEMO, and fundamental research. A 1 MW, tangential neutral beam injector (NBI) was recently installed and promptly extended the TCV parameter range, with record ion temperatures and toroidal rotation velocities and measurable neutral-beam current drive. ITER-relevant scenario development has received particular attention, with strategies aimed at maximizing performance through optimized discharge trajectories to avoid MHD instabilities, such as peeling-ballooning and neoclassical tearing modes. Experiments on exhaust physics have focused particularly on detachment, a necessary step to a DEMO reactor, in a comprehensive set of conventional and advanced divertor concepts. The specific theoretical prediction of an enhanced radiation region between the two X-points in the low-field-side snowflake-minus configuration was experimentally confirmed. Fundamental investigations of the power decay length in the scrape-off layer (SOL) are progressing rapidly, again in widely varying configurations and in both D and He plasmas; in particular, the double decay length in L-mode limited plasmas was found to be replaced by a single length at high SOL resistivity. Experiments on disruption mitigation by massive gas injection and electron-cyclotron resonance heating (ECRH) have begun in earnest, in parallel with studies of runaway electron generation and control, in both stable and disruptive conditions; a quiescent runaway beam carrying the entire electrical current appears to develop in some cases. Developments in plasma control have benefited from progress in individual controller design and have evolved steadily towards controller integration, mostly within an environment supervised by a tokamak profile control simulator. TCV has demonstrated effective wall conditioning with ECRH in He in support of the preparations for JT-60SA operation.
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| 7. |
- Marco, Aitor, et al.
(author)
-
A Variable Structure Control Scheme Proposal for the Tokamak a Configuration Variable
- 2019
-
In: Complexity. - : Hindawi Publishing Corporation. - 1076-2787 .- 1099-0526.
-
Journal article (peer-reviewed)abstract
- Fusion power is the most significant prospects in the long-term future of energy in the sense that it composes a potentially clean, cheap, and unlimited power source that would substitute the widespread traditional nonrenewable energies, reducing the geographical dependence on their sources as well as avoiding collateral environmental impacts. Although the nuclear fusion research started in the earlier part of 20th century and the fusion reactors have been developed since the 1950s, the fusion reaction processes achieved have not yet obtained net power, since the generated plasma requires more energy to achieve and remain in necessary particular pressure and temperature conditions than the produced profitable energy. For this purpose, the plasma has to be confined inside a vacuum vessel, as it is the case of the Tokamak reactor, which consists of a device that generates magnetic fields within a toroidal chamber, being one of the most promising solutions nowadays. However, the Tokamak reactors still have several issues such as the presence of plasma instabilities that provokes a decay of the fusion reaction and, consequently, a reduction in the pulse duration. In this sense, since long pulse reactions are the key to produce net power, the use of robust and fast controllers arises as a useful tool to deal with the unpredictability and the small time constant of the plasma behavior. In this context, this article focuses on the application of robust control laws to improve the controllability of the plasma current, a crucial parameter during the plasma heating and confinement processes. In particular, a variable structure control scheme based on sliding surfaces, namely, a sliding mode controller (SMC) is presented and applied to the plasma current control problem. In order to test the validity and goodness of the proposed controller, its behavior is compared to that of the traditional PID schemes applied in these systems, using the RZIp model for the Tokamak a Configuration Variable (TCV) reactor. The obtained results are very promising, leading to consider this controller as a strong candidate to enhance the performance of the PID-based controllers usually employed in this kind of systems.
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| 8. |
- Rheinbay, E, et al.
(author)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
-
Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 9. |
- Teumer, A., et al.
(author)
-
Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
- 2016
-
In: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824
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Journal article (peer-reviewed)abstract
- The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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| 10. |
- Christiansen, J. S., et al.
(author)
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Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
-
In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
-
Journal article (peer-reviewed)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Carlevaro-Fita, J, et al.
(author)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
-
In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
-
Journal article (peer-reviewed)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 15. |
- Johannsson, Gudmundur, 1960, et al.
(author)
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Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
- 2018
-
In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:3
-
Journal article (peer-reviewed)abstract
- Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
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| 16. |
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| 17. |
- Sodergren, S. C., et al.
(author)
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International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer–Specific Health-Related Quality of Life Questionnaire
- 2023
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In: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 115:5, s. 1155-1164
-
Journal article (peer-reviewed)abstract
- Purpose: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. Methods and Materials: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. Results: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. Conclusions: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.
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| 18. |
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| 19. |
- Allen, D. B., et al.
(author)
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GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
- 2016
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
-
Journal article (peer-reviewed)abstract
- Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 20. |
- Barrio, Isabel C., et al.
(author)
-
Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome
- 2017
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In: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 40:11, s. 2265-2278
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Journal article (peer-reviewed)abstract
- Chronic, low intensity herbivory by invertebrates, termed background herbivory, has been understudied in tundra, yet its impacts are likely to increase in a warmer Arctic. The magnitude of these changes is however hard to predict as we know little about the drivers of current levels of invertebrate herbivory in tundra. We assessed the intensity of invertebrate herbivory on a common tundra plant, the dwarf birch (Betula glandulosa-nana complex), and investigated its relationship to latitude and climate across the tundra biome. Leaf damage by defoliating, mining and gall-forming invertebrates was measured in samples collected from 192 sites at 56 locations. Our results indicate that invertebrate herbivory is nearly ubiquitous across the tundra biome but occurs at low intensity. On average, invertebrates damaged 11.2% of the leaves and removed 1.4% of total leaf area. The damage was mainly caused by external leaf feeders, and most damaged leaves were only slightly affected (12% leaf area lost). Foliar damage was consistently positively correlated with mid-summer (July) temperature and, to a lesser extent, precipitation in the year of data collection, irrespective of latitude. Our models predict that, on average, foliar losses to invertebrates on dwarf birch are likely to increase by 6-7% over the current levels with a 1 degrees C increase in summer temperatures. Our results show that invertebrate herbivory on dwarf birch is small in magnitude but given its prevalence and dependence on climatic variables, background invertebrate herbivory should be included in predictions of climate change impacts on tundra ecosystems.
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| 21. |
- Barrio, Isabel C., et al.
(author)
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Publisher Correction to : Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome (vol 40, pg 2265, 2017)
- 2018
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In: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 41:8, s. 1653-1654
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Journal article (peer-reviewed)abstract
- The above mentioned article was originally scheduled for publication in the special issue on Ecology of Tundra Arthropods with guest editors Toke T. Hoye . Lauren E. Culler. Erroneously, the article was published in Polar Biology, Volume 40, Issue 11, November, 2017. The publisher sincerely apologizes to the guest editors and the authors for the inconvenience caused.
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| 22. |
- Hansen, Lea B.S., et al.
(author)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 23. |
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| 24. |
- Munch Roager, Henrik, et al.
(author)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Journal article (peer-reviewed)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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| 25. |
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| 26. |
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| 27. |
- Vogel, N, et al.
(author)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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In: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
-
Journal article (peer-reviewed)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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| 28. |
- Vogel, N, et al.
(author)
-
Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
-
In: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
-
Journal article (peer-reviewed)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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| 29. |
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| 30. |
- Binder, G, et al.
(author)
-
GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice
- 2020
-
In: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 92:3, s. 150-156
-
Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. <b><i>Methods:</i></b> A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. <b><i>Results:</i></b> National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. <b><i>Conclusions:</i></b> GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.
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| 31. |
- Buunen, M, et al.
(author)
-
COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.
- 2009
-
In: Danish medical bulletin. - 1603-9629 .- 0907-8916. ; 56:2, s. 89-91
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. Trial registration: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
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| 32. |
- Collett-Solberg, Paulo F., et al.
(author)
-
Diagnosis, Genetics, and Therapy of Short Stature in Children : A Growth Hormone Research Society International Perspective
- 2019
-
In: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 92:1, s. 1-14
-
Journal article (peer-reviewed)abstract
- The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
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| 33. |
- Dean, J. M., et al.
(author)
-
A Critical Review of Models of Perinatal Infection
- 2015
-
In: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 37:4-5, s. 289-304
-
Research review (peer-reviewed)abstract
- One of the central, unanswered questions in perinatology is why preterm infants continue to have such poor long-term neurodevelopmental, cognitive and learning outcomes, even though severe brain injury is now rare. There is now strong clinical evidence that one factor underlying disability may be infection, as well as nonspecific inflammation, during fetal and early postnatal life. In this review, we examine the experimental evidence linking both acute and chronic infection/inflammation with perinatal brain injury and consider key experimental determinants, including the microglia response, relative brain and immune maturity and the pattern of exposure to infection. We highlight the importance of the origin and derivation of the bacterial cell wall component lipopolysaccharide. Such experimental paradigms are essential to determine the precise time course of the inflammatory reaction and to design targeted neuroprotective strategies to protect the perinatal brain from infection and inflammation. (C) 2015 S. Karger AG, Basel
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| 34. |
- Galinsky, R., et al.
(author)
-
Magnesium Is Not Consistently Neuroprotective for Perinatal Hypoxia-Ischemia in Term-Equivalent Models in Preclinical Studies: A Systematic Review
- 2014
-
In: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 36:2, s. 73-82
-
Journal article (peer-reviewed)abstract
- There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO4) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but that it has no effect on death or disability. Because of this inconsistency, it remains controversial whether MgSO4 is clinically neuroprotective and, thus, it is unclear whether it would be appropriate to test MgSO4 for treatment of encephalopathy in term infants. We therefore systematically reviewed the preclinical evidence for neuroprotection with MgSO4 before or after hypoxic-ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The outcomes were highly inconsistent between studies. Although there were differences in dose and timing of administration, there was evidence that beneficial effects of MgSO4 were associated with confounding mild hypothermia and, strikingly, the studies that included rigorous maintenance of environmental temperature or body temperature consistently suggested a lack of effect. On balance, these preclinical studies suggest that peripherally administered MgSO4 is unlikely to be neuroprotective. Rigorous testing in translational animal models of perinatal HIE is needed before MgSO4 should be considered in clinical trials for encephalopathy in term infants. (C) 2014 S. Karger AG, Basel
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| 35. |
- Johnson, Linda S B, et al.
(author)
-
ST segment depression on 24-hour electrocardiography predicts incident atrial fibrillation in two population-based cohorts
- 2018
-
In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 20:3, s. 429-434
-
Journal article (peer-reviewed)abstract
- Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development.Methods and results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women.Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Weston, David J., et al.
(author)
-
The Sphagnome Project : enabling ecological and evolutionary insights through a genus-level sequencing project
- 2018
-
In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 217:1, s. 16-25
-
Journal article (other academic/artistic)abstract
- Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even 'extend' to influence community structure and ecosystem level processes. Progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Thus, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. Here we introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration, biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses.
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| 41. |
- Williams, S., et al.
(author)
-
Comparison of climate signals obtained from encrusting and free-living rhodolith coralline algae
- 2018
-
In: Chemical Geology. - : Elsevier BV. - 0009-2541. ; 476, s. 418-428
-
Journal article (peer-reviewed)abstract
- Coralline algae have been used for sclerochronological studies throughout the last decade. These studies have focused on two different growth morphologies of the photosynthetic coralline algae: massive crusts forming small buildups on hard substrate, and free-living branching algal nodules, known as rhodoliths. The latter are generally found on soft-substrate, where they are frequently overturned by water movement and bottom feeding organisms, leaving one side of the rhodolith partially buried in the sediment at any given time. Here we test whether either of these growth morphologies is more suitable for proxy reconstructions by comparing Mg/Ca ratios - a temperature proxy - in multiple replicates of rhodoliths of Lithothamnion glaciale and in rhodoliths as well as encrusting specimens of Clathromorphum compactum. With both species being widespread throughout the Temperate and Arctic regions, we have chosen two North Atlantic localities at Nuuk Fjord, Greenland (Subarctic), and off the southeastern coast of Newfoundland, Canada (Temperate), for this study. Two to three Mg/Ca ratio transects spanning 18 years of growth were analysed on multiple specimens with encrusting morphologies and along different sides of rhodoliths using laser ablation inductively coupled mass spectrometry and compared to remotely sensed sea surface temperature (SST) data. The length of the common time span used for comparison was limited by growth interruptions in rhodoliths. Furthermore, our comparison is based on the assumption that rhodolith growth increments are annual - an assumption that has recently been challenged by mesocosm studies. Monthly Mg/Ca values from multiple transects within each individual were compared and in samples from Nuuk fjord significant correlations were found in 4 of 4 encrusting C. compactum, 4 of 4 C. compactum rhodoliths, and 2 of 3 L. glaciale rhodoliths. In Newfoundland significant correlations were found in 6 of 6 encrusting C. compactum comparisons (average: r = 0.61, p < 0.001), and in 6 of 6 L. glaciale rhodolith comparisons (average: r = 0.43, p < 0.001) for monthly resolved time series. The monthly Mg/Ca ratios (n = 216) from each morphology were compared with instrumental Reynolds SST yielding the following correlations: encrusting C. compactum (r = 0.64, p < 0.001), C. compactum rhodolith (r = 0.62, p < 0.001) and L. glaciale (r = 0.58, p < 0.001). In Newfoundland both morphologies indicate a similar strength in recording SST: encrusting C. compactum (r = 0.85, p < 0.001) and rhodolith-forming L. glaciale (r = 0.84, p < 0.001). In summary, Mg/Ca ratios derived from both coralline algal growth forms can yield SST information, however, massive encrusting forms generally yield higher correlations to SST than transects measured on individual rhodoliths, which only allowed for the generation of short uninterrupted time series due to frequent growth irregularities.
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| 42. |
- Williams, S., et al.
(author)
-
Coralline Algae Archive Fjord Surface Water Temperatures in Southwest Greenland
- 2018
-
In: Journal of Geophysical Research-Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953. ; 123:8, s. 2617-2626
-
Journal article (peer-reviewed)abstract
- One of the most dramatic signs of ongoing global change is the mass loss of the Greenland Ice Sheet and the resulting rise in sea level, whereby most of the recent ice sheet mass loss can be attributed to an increase in meltwater runoff. The retreat and thinning of Greenland glaciers has been caused by rising air and ocean temperatures over the past decades. Despite the global scale impact of the changing ice sheet balance, estimates of glacial runoff in Greenland rarely extend past several decades, thus limiting our understanding of long-term glacial response to temperature. Here we present a 42-year long annually resolved red coralline algal Mg/Ca proxy temperature record from a southwestern Greenland fjord, with temperature ranging from 1.5 to 4 degrees C (standard error = 1.06 degrees C). This temperature time series in turn tracks the general trend of glacial runoff from four West Greenland glaciers discharging freshwater into the fjord (all p < 0.001). The algal time series further exhibits significant correlations to Irminger Sea temperature patterns, which are transmitted to western Greenland fjords via the West Greenland Current. The 42-year long record demonstrates the potential of annual increment forming coralline algae, which are known to live up to 650 years and which are abundant along the Greenland coastline, for reconstructing time series of sea surface temperature.
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| 43. |
- Williams, S., et al.
(author)
-
Reprint of Comparison of climate signals obtained from encrusting and free-living rhodolith coralline algae
- 2019
-
In: Chemical Geology. - : Elsevier BV. - 0009-2541. ; 526, s. 175-185
-
Journal article (peer-reviewed)abstract
- Coralline algae have been used for sclerochronological studies throughout the last decade. These studies have focused on two different growth morphologies of the photosynthetic coralline algae: massive crusts forming small buildups on hard substrate, and free-living branching algal nodules, known as rhodoliths. The latter are generally found on soft-substrate, where they are frequently overturned by water movement and bottom feeding organisms, leaving one side of the rhodolith partially buried in the sediment at any given time. Here we test whether either of these growth morphologies is more suitable for proxy reconstructions by comparing Mg/Ca ratios - a temperature proxy - in multiple replicates of rhodoliths of Lithothamnion glaciale and in rhodoliths as well as encrusting specimens of Clathromorphum compactum. With both species being widespread throughout the Temperate and Arctic regions, we have chosen two North Atlantic localities at Nuuk Fjord, Greenland (Subarctic), and off the southeastern coast of Newfoundland, Canada (Temperate), for this study. Two to three Mg/Ca ratio transects spanning 18 years of growth were analysed on multiple specimens with encrusting morphologies and along different sides of rhodoliths using laser ablation inductively coupled mass spectrometry and compared to remotely sensed sea surface temperature (SST) data. The length of the common time span used for comparison was limited by growth interruptions in rhodoliths. Furthermore, our comparison is based on the assumption that rhodolith growth increments are annual - an assumption that has recently been challenged by mesocosm studies. Monthly Mg/Ca values from multiple transects within each individual were compared and in samples from Nuuk fjord significant correlations were found in 4 of 4 encrusting C. compactum, 4 of 4 C. compactum rhodoliths, and 2 of 3 L. glaciale rhodoliths. In Newfoundland significant correlations were found in 6 of 6 encrusting C. compactum comparisons (average: r = 0.61, p < 0.001), and in 6 of 6 L. glaciale rhodolith comparisons (average: r= 0.43, p < 0.001) for monthly resolved time series. The monthly Mg/Ca ratios (n = 216) from each morphology were compared with instrumental Reynolds SST yielding the following correlations: encrusting C. compactum (r = 0.64, p < 0.001), C. compactum rhodolith (r = 0.62, p < 0.001) and L. glaciale (r = 0.58, p < 0.001). In Newfoundland both morphologies indicate a similar strength in recording SST: encrusting C. compactum (r = 0.85, p < 0.001) and rhodolith-forming L. glaciale (r= 0.84, p < 0.001). In summary, Mg/Ca ratios derived from both coralline algal growth forms can yield SST information, however, massive encrusting forms generally yield higher correlations to SST than transects measured on individual rhodoliths, which only allowed for the generation of short uninterrupted time series due to frequent growth irregularities.
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| 44. |
- Andersen, Felicie F., et al.
(author)
-
Assembly and structural analysis of a covalently closed nano-scale DNA cage
- 2008
-
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 36:4, s. 1113-1119
-
Journal article (peer-reviewed)abstract
- The inherent properties of DNA as a stable polymer with unique affinity for partner mols. detd. by the specific Watson-Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnol. Here we present the design, construction and structural anal. of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helixes that assembles from eight oligonucleotides with a yield of .apprx.30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-mols. to enable their investigation in certain harmful environments or even allow their organization into higher order structures.
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| 45. |
- Bager, Ninna, et al.
(author)
-
Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia : A NOPHO-DBH-AML study
- 2018
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 183:4, s. 618-628
-
Journal article (peer-reviewed)abstract
- Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2.1 and 3.3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1.43, P = 0.03) and overall survival (OS; HR 1.48, P = 0.01). MK was associated with a poor EFS (HR 1.57, P = 0.03) but did not show an inferior OS compared to non-MK patients (HR 1.14, P = 0.62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.
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| 46. |
- Beck, Astrid L, et al.
(author)
-
Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study
- 2024
-
In: International Journal of Cancer. - 0020-7136. ; 154:1, s. 71-80
-
Journal article (peer-reviewed)abstract
- Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
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| 47. |
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| 48. |
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| 49. |
- Bergman, Åke, et al.
(author)
-
Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
-
In: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
-
Journal article (peer-reviewed)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 50. |
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