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Sökning: WFRF:(Nicol P.)

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1.
  • Niemi, MEK, et al. (författare)
  • 2021
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  • Kanai, M, et al. (författare)
  • 2023
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  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Tidskriftsartikel (refereegranskat)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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  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)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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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)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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22.
  • Block, Keith I., et al. (författare)
  • Designing a broad-spectrum integrative approach for cancer prevention and treatment
  • 2015
  • Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
  • Forskningsöversikt (refereegranskat)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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  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)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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  • Flores, H., et al. (författare)
  • Impact of climate change on Antarctic krill
  • 2012
  • Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
  • Tidskriftsartikel (refereegranskat)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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  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)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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  • Nicol, S., et al. (författare)
  • Ocean Futures for the World’s Largest Yellowfin Tuna Population Under the Combined Effects of Ocean Warming and Acidification
  • 2022
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The impacts of climate change are expected to have profound effects on the fisheries of the Pacific Ocean, including its tuna fisheries, the largest globally. This study examined the combined effects of climate change on the yellowfin tuna population using the ecosystem model SEAPODYM. Yellowfin tuna fisheries in the Pacific contribute significantly to the economies and food security of Pacific Island Countries and Territories and Oceania. We use an ensemble of earth climate models to project yellowfin populations under a high greenhouse gas emissions (IPCC RCP8.5) scenario, which includes, the combined effects of a warming ocean, increasing acidification and changing ocean chemistry. Our results suggest that the acidification impact will be smaller in comparison to the ocean warming impact, even in the most extreme ensemble member scenario explored, but will have additional influences on yellowfin tuna population dynamics. An eastward shift in the distribution of yellowfin tuna was observed in the projections in the model ensemble in the absence of explicitly accounting for changes in acidification. The extent of this shift did not substantially differ when the three-acidification induced larval mortality scenarios were included in the ensemble; however, acidification was projected to weaken the magnitude of the increase in abundance in the eastern Pacific. Together with intensive fishing, these potential changes are likely to challenge the global fishing industry as well as the economies and food systems of many small Pacific Island Countries and Territories. The modelling framework applied in this study provides a tool for evaluating such effects and informing policy development.
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  • Schulman, S., et al. (författare)
  • 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
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:4, s. 734-742
  • Tidskriftsartikel (refereegranskat)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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  • Bjurstrom, M. F., et al. (författare)
  • Neurophysiological and Clinical Effects of Laparoscopic Retroperitoneal Triple Neurectomy in Patients with Refractory Postherniorrhaphy Neuropathic Inguinodynia
  • 2017
  • Ingår i: Pain Pract. ; 17:4, s. 447-459
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic postherniorrhaphy inguinal pain (CPIP) is a complex, major health problem. In the absence of recurrence or meshoma, laparoscopic retroperitoneal triple neurectomy (LRTN) has emerged as an effective surgical treatment of CPIP. METHODS: This prospective pilot study evaluated the neurophysiological and clinical effects of LRTN. Ten consecutive adult CPIP patients with unilateral predominantly neuropathic inguinodynia underwent three comprehensive quantitative sensory testing (QST) assessments (preoperative, immediate postoperative, and late postoperative). Pain severity, health-related function, and sleep quality were assessed over the course of a 6-month follow-up period. RESULTS: QST revealed marked increases in mechanical, pressure, thermal, and pain thresholds in the areas with maximum pain prior to LRTN surgery for the immediate (P < 0.01; mean 160.9 minutes, range 103 to 255 minutes after extubation) and late postoperative (P < 0.05; mean 27.9 days, range 14 to 78 days after surgery) assessments compared to baseline. Wind-up phenomena were eliminated postoperatively. LRTN provided robust group-level improvements of all clinical measures. No preoperative QST variables were found to be predictive of surgical outcomes. The positive change in heat pain threshold (preoperative compared to late postoperative) showed significant positive correlations with improvements of pain scores and function. CONCLUSIONS: LRTN may produce immediate, profound, and consistent positive effects across multiple mechanical, pressure, and thermal QST variables, and marked improvements of clinical outcomes in selected CPIP patients. These data contribute to the understanding of mechanisms involved in the success of LRTN. Large, high-powered studies are warranted to determine whether preoperative or repeated longitudinal QST may guide patient selection and predict effectiveness of LRTN.
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36.
  • Bjurstrom, M. F., et al. (författare)
  • Pain control following inguinal herniorrhaphy : current perspectives
  • 2014
  • Ingår i: J Pain Res. ; 7, s. 277-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Inguinal hernia repair is one of the most common surgeries performed worldwide. With the success of modern hernia repair techniques, recurrence rates have significantly declined, with a lower incidence than the development of chronic postherniorrhaphy inguinal pain (CPIP). The avoidance of CPIP is arguably the most important clinical outcome and has the greatest impact on patient satisfaction, health care utilization, societal cost, and quality of life. The etiology of CPIP is multifactorial, with overlapping neuropathic and nociceptive components contributing to this complex syndrome. Treatment is often challenging, and no definitive treatment algorithm exists. Multidisciplinary management of this complex problem improves outcomes, as treatment must be individualized. Current medical, pharmacologic, interventional, and surgical management strategies are reviewed.
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  • Bjurstrom, M. F., et al. (författare)
  • Quantitative validation of sensory mapping in persistent postherniorrhaphy inguinal pain patients undergoing triple neurectomy
  • 2017
  • Ingår i: Hernia. ; 21:2, s. 207-214
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Neurectomy of the inguinal nerves may be considered for selected refractory cases of chronic postherniorrhaphy inguinal pain (CPIP). There is to date a paucity of easily applicable clinical tools to identify neuropathic pain and examine the neurosensory effects of remedial surgery. The present quantitative sensory testing (QST) pilot study evaluates a sensory mapping technique. METHODS: Longitudinal (preoperative, immediate postoperative, and late postoperative) dermatomal sensory mapping and a comprehensive QST protocol were conducted in CPIP patients with unilateral, predominantly neuropathic inguinodynia presenting for triple neurectomy (n = 13). QST was conducted in four areas on the affected, painful side and in one contralateral comparison site. QST variables were compared according to sensory mapping outcomes: (o)/normal sensation, (+)/pain, and (-)/numbness. Diagnostic ability of the sensory mapping outcomes to detect QST-assessed allodynia or hypoesthesia was estimated through calculation of specificity and sensitivity values. RESULTS: Preoperatively, patients exhibited mechanical hypoesthesia and allodynia and pressure allodynia and hyperalgesia in painful areas mapped (+) (p < .05); sensory mapping outcome (+) demonstrated high ability to detect mechanical allodynia [sensitivity 0.74 (95% CI 0.61-0.86), specificity 0.94 (0.84-1.00)] and pressure allodynia [sensitivity 0.96 (0.89-1.00), specificity 1.00 (1.00-1.00)], but not thermal allodynia. Postoperatively, mapped areas of numbness (-) were associated with mechanical and thermal hypoesthesia (p < .05); (-) showed high sensitivity and specificity to detect mechanical and cold hypoesthesia. CONCLUSIONS: Sensory mapping provides an accurate clinical neuropathic assessment with strong correlation to QST findings of preoperative mechanical and pressure allodynia, and postoperative mechanical and thermal hypoesthesia in CPIP patients undergoing neurectomy.
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  • Bromhead, D., et al. (författare)
  • The potential impact of ocean acidification on eggs and larvae of the Yellowfin Tuna.
  • 2015
  • Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645. ; 113, s. 268-279
  • Tidskriftsartikel (refereegranskat)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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  • Care, O., et al. (författare)
  • Creating leadership collectives for sustainability transformations
  • 2021
  • Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 16:2, s. 703-708
  • Tidskriftsartikel (refereegranskat)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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40.
  • Dance, Sarah L., et al. (författare)
  • Improvements in Forecasting Intense Rainfall : Results from the FRANC (Forecasting Rainfall Exploiting New Data Assimilation Techniques and Novel Observations of Convection) Project
  • 2019
  • Ingår i: Atmosphere. - : MDPI. - 2073-4433. ; 10:3
  • Forskningsöversikt (refereegranskat)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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41.
  • Frommel, A. Y., et al. (författare)
  • Ocean acidification has lethal and sub-lethal effects on larval development of yellowfin tuna, Thunnus albacares
  • 2016
  • Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 482, s. 18-24
  • Tidskriftsartikel (refereegranskat)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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42.
  • Hamilton, P. B., et al. (författare)
  • Population-level consequences for wild fish exposed to sublethal concentrations of chemicals : a critical review
  • 2016
  • Ingår i: Fish and Fisheries. - : Wiley. - 1467-2960 .- 1467-2979. ; 17:3, s. 545-566
  • Forskningsöversikt (refereegranskat)abstract
    • Concentrated chemical spills have been shown to impact adversely on fish populations and even cause localized population extinctions. Evaluating population-level impacts of sublethal exposure concentrations is, however, complex and confounded by other environmental pressures. Applying effect measures derived from laboratory-based chemical exposures to impacts in wild fish populations is constrained by uncertainty on how biochemical response measures (biomarkers) translate into health outcomes, lack of available data for chronic exposures and the many uncertainties in available fish population models. Furthermore, wild fish show phenotypic plasticity and local adaptations can occur that adds geographic and temporal variance on responses. Such population-level factors are rarely considered in the chemical risk assessment process and can probably be derived only from studies on wild fish. Molecular technologies, including microsatellite and SNP genotyping, and RNASeq for gene expression studies, are advancing our understanding of mechanisms of eco-toxicological response, tolerance, adaptation and selection in wild populations. We examine critically the application of such approaches with examples including using microsatellites that has identified roach (Rutilus rutilus) populations living in rivers contaminated with sewage effluents that are self-sustaining, and studies of stickleback (Gasterosteus aculeatus) and killifish (Fundulus heteroclitus) that have identified genomic regions under selection putatively related to pollution tolerance. Integrating data on biological effects between laboratory-based studies and wild populations, and building understanding on adaptive responses to sublethal exposure are some of the priority research areas for more effective evaluation of population risks and resilience to contaminant exposure.
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44.
  • Malmberg, K, et al. (författare)
  • 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
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier Inc.. - 0735-1097 .- 1558-3597. ; 26:1, s. 57-65
  • Tidskriftsartikel (refereegranskat)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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46.
  • Nicol, P, et al. (författare)
  • Contrast agent nephropathy
  • 2004
  • Ingår i: EUROPEAN HEART JOURNAL. - : Oxford University Press (OUP). - 0195-668X. ; 25:15, s. 1369-1369
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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47.
  • Rosser, Neil, et al. (författare)
  • Hybrid speciation driven by multilocus introgression of ecological traits
  • 2024
  • Ingår i: Nature. - 0028-0836. ; 628, s. 811-817
  • Tidskriftsartikel (refereegranskat)abstract
    • Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific traits to examine a case of hybrid speciation in Heliconius butterflies. We show that Heliconius elevatus is a hybrid species that is sympatric with both parents and has persisted as an independently evolving lineage for at least 180,000 years. This is despite pervasive and ongoing gene flow with one parent, Heliconius pardalinus, which homogenizes 99% of their genomes. The remaining 1% introgressed from the other parent, Heliconius melpomene, and is scattered widely across the H. elevatus genome in islands of divergence from H. pardalinus. These islands contain multiple traits that are under disruptive selection, including colour pattern, wing shape, host plant preference, sex pheromones and mate choice. Collectively, these traits place H. elevatus on its own adaptive peak and permit coexistence with both parents. Our results show that speciation was driven by introgression of ecological traits, and that speciation with gene flow is possible with a multilocus genetic architecture.
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