| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 11. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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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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| 12. |
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| 14. |
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| 15. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 16. |
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| 17. |
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- 2019
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Journal article (peer-reviewed)
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| 18. |
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| 19. |
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| 20. |
- Block, Keith I., et al.
(author)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Research review (peer-reviewed)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 21. |
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| 22. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Craddock, Nick, et al.
(author)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Journal article (peer-reviewed)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 27. |
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| 28. |
- Flores, H., et al.
(author)
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Impact of climate change on Antarctic krill
- 2012
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In: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
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Journal article (peer-reviewed)abstract
- Antarctic krill Euphausia superba (hereafter 'krill') occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has in creased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved. [GRAPHICS] .
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| 29. |
- Schulman, S., et al.
(author)
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Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months
- 2006
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:4, s. 734-742
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Journal article (peer-reviewed)abstract
- Background: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. Aim: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. Methods: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. Results: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent gering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83, 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28, 95% CI 1.00-1.56).The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. Conclusion: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed. © 2006 International Society on Thrombosis and Haemostasis.
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| 30. |
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| 31. |
- Bromhead, D., et al.
(author)
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The potential impact of ocean acidification on eggs and larvae of the Yellowfin Tuna.
- 2015
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In: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645. ; 113, s. 268-279
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Journal article (peer-reviewed)abstract
- Anthropogenic carbon dioxide (CO2) emissions are resulting in increasing absorption of CO2 by the earth's oceans, which has led to a decline in ocean pH, a process known as ocean acidification (OA). Evidence suggests that OA may have the potential to affect the distribution and population dynamics of many marine organisms. Early life history processes (e.g. fertilization) and stages (eggs, larvae, juveniles) may be relatively more vulnerable to potential OA impacts, with implications for recruitment in marine populations. The potential impact of OA upon tuna populations has not been investigated, although tuna are key components of pelagic ecosystems and, in the Pacific Ocean, form the basis of one of the largest and most valuable fisheries in the world. This paper reviews current knowledge of potential OA impacts on fish and presents results from a pilot study investigating how OA may affect eggs and larvae of yellowfin tuna, Thunnus albacares. Two separate trials were conducted to test the impact of pCO2 on yellowfin egg stage duration, larval growth and survival. The pCO2 levels tested ranged from present day ($400 μatm) to levels predicted to occur in some areas of the spawning habitat within the next 100 years (o2500 μatm) to 300 years ($ o5000 μatm) to much more extreme levels ($10,000 μatm). In trial 1, there was evidence for significantly reduced larval survival (at mean pCO2 levelsZ4730 μatm) and growth (at mean pCO2 levels Z 2108 μatm), while egg hatch time was increased at extreme pCO2 levelsZ10,000 μatm (nintermediate levels were not tested). In trial 2, egg hatch times were increased at mean pCO2 levelsZ1573 μatm, but growth was only impacted at higher pCO2 (Z8800 μatm) and there was no relationship with survival. Unstable ambient conditions during trial 2 are likely to have contributed to the difference in results between trials. Despite the technical challenges with these experiments, there is a need for future empirical work which can in turn support modeling-based approaches to assess how OA will affect the ecologically and economically important tropical tuna resources.
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| 32. |
- Frommel, A. Y., et al.
(author)
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Ocean acidification has lethal and sub-lethal effects on larval development of yellowfin tuna, Thunnus albacares
- 2016
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In: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 482, s. 18-24
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Journal article (peer-reviewed)abstract
- Ocean acidification (OA), the process by which increasing atmospheric CO2 is absorbed by the ocean, lowering the pH of surface waters, has been shown to affect many marine organisms negatively. It has been suggested that organisms from regions with naturally low pH waters, such as upwelling areas, could serve as models for future effects of OA and may be adapted to increased pCO(2) levels. In this study, we examined the effects of OA on yellowfin tuna, a highly pelagic species that spawns in the eastern tropical Pacific, an area that includes regions of strong upwelling events. Larvae reared at decreasing pH levels (pH 8.1, 7.6, 7.3 and 6.9) showed increasing organ damage in the kidney, liver, pancreas, eye and muscle, which correlated with decreased growth and survival. These findings complement earlier studies on organ damage in Atlantic cod and herring larvae and demonstrate that OA may have detrimental effects on fish larvae, regardless of their pre-exposure to low pH waters.
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| 33. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Wang, Zongwei, et al.
(author)
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Broad targeting of angiogenesis for cancer prevention and therapy
- 2015
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In: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; S1044-579X:15, s. 00002-00004
-
Research review (peer-reviewed)abstract
- Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature - is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies.
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| 40. |
- Wexler, J. B., et al.
(author)
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The effect of ocean acidification on otolith morphology in larvae of a tropical, epipelagic fish species, yellowfin tuna (Thunnus albacares)
- 2023
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In: Journal of Experimental Marine Biology and Ecology. - 0022-0981. ; 569
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Journal article (peer-reviewed)abstract
- Increasing ocean acidification is a concern due to its potential effects on the growth, development, and survival of early life stages of tuna in oceanic habitats and on the spatial extent of their suitable nursery habitat. To investigate the potential effects of increasing CO2 on otolith calcification of 9-day old pre-flexion stage yellowfin tuna (Thunnus albacares), an experiment was conducted at the Inter-American Tropical Tuna Commission's Achotines Laboratory in Panama during 2011. Fertilized eggs and larvae were exposed to mean pCO2 levels that ranged from present day (355 mu atm) to two levels predicted to occur in some areas of the Pacific in the near future (2013 and 3321 mu atm), and to an extreme value equivalent to long-term projections for 300 years in the future (9624 mu atm). The results indicated significantly larger otoliths (in area and perimeter) with significant, and increasing, fluctuating asymmetry at acidification levels similar to those projected for the near future and long-term. Otoliths increased significantly in size despite a significant decrease in somatic length with increasing pCO2. A consistent correlation between otolith and somatic growth of yellowfin tuna larvae among treatments was evident (i.e., larger otoliths were still associated with larger larvae within a treatment). The observed changes in otolith morphology with increasing ocean acidification have the potential to indirectly affect larval survival through dysfunction of the mechanosensory organs, but this remains to be verified in yellowfin tuna larvae.
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| 41. |
- Baker, Kate L., et al.
(author)
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Environmental and spatial characterisation of microbial community composition to inform sampling strategies
- 2009
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In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 41:11, s. 2292-2298
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Journal article (peer-reviewed)abstract
- Soil physicochemical properties and microbial communities are highly heterogeneous and vary widely over spatial scales, necessitating careful consideration of sampling strategies to provide representative and reproducible soil samples across field sites. To achieve this, the study aimed to establish appropriate sampling methodology and to determine links between the variability of parameters, utilising two sampling strategies. The first (design 1) involved extracting 25 cores from random locations throughout the field and pooling them into five sets of five cores. The second (design 2) involved a further 25 cores within five 1 m2 sub-plots. Sub-samples from each sub-plot were pooled in order to determine between and within sub-plot variability. All samples were analysed independently and as pooled sub-samples. Results indicate that pooling spatially separated samples significantly reduced the variability in pH, compared to individual samples. Pooling samples from a small area resulted in lower within sub-plot variability than between sub-plots for pH and bacterial community composition assessed by terminal-restriction fragment length polymorphism analysis. Following multivariate statistical analysis, a large amount of variation in community composition was explained by soil pH, which is remarkable given the relatively small size of the sampling area and minor differences in pH. Moisture content was also important in determining bacterial communities in the random design (design 1). In the 1 m2 sub-plot design (design 2), the spatial location of the plots explained a large degree of the variation in bacterial community composition between plots, which was due to spatial autocorrelation of pH and possible additional environmental parameters. This study emphasises the importance of sampling design for obtaining representative samples from soil.
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| 42. |
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| 43. |
- Care, O., et al.
(author)
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Creating leadership collectives for sustainability transformations
- 2021
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In: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 16:2, s. 703-708
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Journal article (peer-reviewed)abstract
- Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet.
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| 44. |
- Dance, Sarah L., et al.
(author)
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Improvements in Forecasting Intense Rainfall : Results from the FRANC (Forecasting Rainfall Exploiting New Data Assimilation Techniques and Novel Observations of Convection) Project
- 2019
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In: Atmosphere. - : MDPI. - 2073-4433. ; 10:3
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Research review (peer-reviewed)abstract
- The FRANC project (Forecasting Rainfall exploiting new data Assimilation techniques and Novel observations of Convection) has researched improvements in numerical weather prediction of convective rainfall via the reduction of initial condition uncertainty. This article provides an overview of the project's achievements. We highlight new radar techniques: correcting for attenuation of the radar return; correction for beams that are over 90% blocked by trees or towers close to the radar; and direct assimilation of radar reflectivity and refractivity. We discuss the treatment of uncertainty in data assimilation: new methods for estimation of observation uncertainties with novel applications to Doppler radar winds, Atmospheric Motion Vectors, and satellite radiances; a new algorithm for implementation of spatially-correlated observation error statistics in operational data assimilation; and innovative treatment of moist processes in the background error covariance model. We present results indicating a link between the spatial predictability of convection and convective regimes, with potential to allow improved forecast interpretation. The research was carried out as a partnership between University researchers and the Met Office (UK). We discuss the benefits of this approach and the impact of our research, which has helped to improve operational forecasts for convective rainfall events.
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| 45. |
- Giron, S. E., et al.
(author)
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Increased Central Nervous System Interleukin-8 in a Majority Postlaminectomy Syndrome Chronic Pain Population
- 2018
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In: Pain Med. ; 19:5, s. 1033-1043
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Multiple processes have been identified as potential contributors to chronic pain, with increasing evidence illustrating an association with aberrant levels of neuroimmune mediators. The primary objectives of the present study were to examine central nervous system cytokines, chemokines, and growth factors present in a chronic pain population and to explore patterns of the same mediator molecules over time. Secondary objectives explored the relationship of central and peripheral neuroimmune mediators while examining the levels of anxiety, depression, sleep quality, and perception of pain associated with the chronic pain patient experience. METHODS: Cerebrospinal fluid (CSF) from a population of majority postlaminectomy syndrome patients (N = 8) was compared with control CSF samples (N = 30) to assess for significant differences in 10 cytokines, chemokines, and growth factors. The patient population was then followed over time, analyzing CSF, plasma, and psychobehavioral measures. RESULTS: The present observational study is the first to demonstrate increased mean CSF levels of interleukin-8 (IL-8; P < 0.001) in a small population of majority postlaminectomy syndrome patients, as compared with a control population. Over time in pain patients, CSF levels of IL-8 increased significantly (P < 0.001). CONCLUSIONS: These data indicate that IL-8 should be further investigated and psychobehavioral components considered in the overall chronic pain paradigm. Future studies examining the interactions between these factors and IL-8 may identify novel targets for treatment of persistent pain states.
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| 46. |
- Kumar, Ravhi S., et al.
(author)
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Pressure-induced valence change in YbAl3 : A combined high-pressure inelastic x-ray scattering and theoretical investigation
- 2008
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 78:7, s. 075117-
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Journal article (peer-reviewed)abstract
- High-resolution x-ray-absorption (XAS) experiments in the partial fluorescence yield mode (PFY) and resonant inelastic x-ray emission (RXES) measurements were performed on the intermediate-valence compound YbAl3 under pressure of up to 38 GPa. The results of the YbAl3 PFY-XAS and RXES studies show that the valence of Yb increases smoothly from 2.75 at ambient pressure to 2.93 at 38 GPa. In situ angle-dispersive synchrotron high-pressure x-ray-diffraction experiments carried out using a diamond cell at room temperature show that the ambient pressure cubic phase is stable up to 40 GPa. The results obtained from self-interaction corrected local spin density-functional calculations to understand the pressure effect on the Yb valence and compressibility are in good agreement with the experimental results.
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| 47. |
- Malmberg, K, et al.
(author)
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Randomised trial of insuline-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI-Study) Effects on mortality at 1 year
- 1995
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In: Journal of the American College of Cardiology. - : Elsevier Inc.. - 0735-1097 .- 1558-3597. ; 26:1, s. 57-65
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Journal article (peer-reviewed)abstract
- Objectives. We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. Background. Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. Methods. A total of 620 patients were studied : 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for ≥3 months and 314 to conventional therapy. Results. The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 ± 4.1 to 9.6 ± 3.3 mmol/liter (mean ± SD) in the infusion group during the 1st 24 h, and from 15.7 ± 4.2 to 11.7 ± 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046] ; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). Conclusions. Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.
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- Middleton, Anna, et al.
(author)
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Global Public Perceptions of Genomic Data Sharing : What Shapes the Willingness to Donate DNA and Health Data?
- 2020
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:4, s. 743-752
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Journal article (peer-reviewed)abstract
- Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.
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- Milne, Richard, et al.
(author)
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Demonstrating trustworthiness when collecting and sharing genomic data : public views across 22 countries
- 2021
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 13:1
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Journal article (peer-reviewed)abstract
- BackgroundPublic trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.MethodsWe analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.ResultsProviding transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.ConclusionsOur findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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