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- Van den Brink, P. J., et al.
(author)
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Toward sustainable environmental quality: Priority research questions for Europe
- 2018
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In: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 37:9, s. 2281-2295
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Journal article (peer-reviewed)abstract
- The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon-scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first-step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment. Environ Toxicol Chem 2018;37:2281-2295. (c) 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
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- Castillo, N. A., et al.
(author)
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Understanding pharmaceutical exposure and the potential for effects in marine biota : A survey of bonefish (Albula vulpes) across the Caribbean Basin
- 2024
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In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 349
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Journal article (peer-reviewed)abstract
- Most research on pharmaceutical presence in the environment to date has focused on smaller scale assessments of freshwater and riverine systems, relying mainly on assays of water samples, while studies in marine ecosystems and of exposed biota are sparse. This study investigated the pharmaceutical burden in bonefish (Albula vulpes), an important recreational and artisanal fishery, to quantify pharmaceutical exposure throughout the Caribbean Basin. We sampled 74 bonefish from five regions, and analyzed them for 102 pharmaceuticals. We assessed the influence of sampling region on the number of pharmaceuticals, pharmaceutical assemblage, and risk of pharmacological effects. To evaluate the risk of pharmacological effects at the scale of the individual, we proposed a metric based on the human therapeutic plasma concentration (HTPC), comparing measured concentrations to a threshold of 1/3 the HTPC for each pharmaceutical. Every bonefish had at least one pharmaceutical, with an average of 4.9 and a maximum of 16 pharmaceuticals in one individual. At least one pharmaceutical was detected in exceedance of the 1/3 HTPC threshold in 39% of bonefish, with an average of 0.6 and a maximum of 11 pharmaceuticals exceeding in a Key West individual. The number of pharmaceuticals (49 detected in total) differed across regions, but the risk of pharmacological effects did not (23 pharmaceuticals exceeded the 1/3 HTPC threshold). The most common pharmaceuticals were venlafaxine (43 bonefish), atenolol (36), naloxone (27), codeine (27), and trimethoprim (24). Findings suggest that pharmaceutical detections and concentration may be independent, emphasizing the need to monitor risk to biota regardless of exposure diversity, and to focus on risk quantified at the individual level. This study supports the widespread presence of pharmaceuticals in marine systems and shows the utility of applying the HTPC to assess the potential for pharmacological effects, and thus quantify impact of exposure at large spatial scales.
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- Hetland, M. L., et al.
(author)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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In: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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- Silva, CS, et al.
(author)
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High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
- 2021
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 727300-
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Journal article (peer-reviewed)abstract
- Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
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- Venero, J. L., et al.
(author)
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ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
- 2023
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In: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
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Journal article (other academic/artistic)abstract
- Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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- Conrad, J L, et al.
(author)
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Behavioural syndromes in fishes : a review with implications for ecology and fisheries management
- 2011
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In: Journal of Fish Biology. - : Wiley. - 0022-1112 .- 1095-8649. ; 78:2, s. 395-435
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Journal article (peer-reviewed)abstract
- This review examines the contribution of research on fishes to the growing field of behavioural syndromes. Current knowledge of behavioural syndromes in fishes is reviewed with respect to five main axes of animal personality: (1) shyness-boldness, (2) exploration-avoidance, (3) activity, (4) aggressiveness and (5) sociability. Compared with other taxa, research on fishes has played a leading role in describing the shy-bold personality axis and has made innovative contributions to the study of the sociability dimension by incorporating social network theory. Fishes are virtually the only major taxon in which behavioural correlations have been compared between populations. This research has guided the field in examining how variation in selection regime may shape personality. Recent research on fishes has also made important strides in understanding genetic and neuroendocrine bases for behavioural syndromes using approaches involving artificial selection, genetic mapping, candidate gene and functional genomics. This work has illustrated consistent individual variation in highly complex neuroendocrine and gene expression pathways. In contrast, relatively little work on fishes has examined the ontogenetic stability of behavioural syndromes or their fitness consequences. Finally, adopting a behavioural syndrome framework in fisheries management issues including artificial propagation, habitat restoration and invasive species, may promote restoration success. Few studies, however, have examined the ecological relevance of behavioural syndromes in the field. Knowledge of how behavioural syndromes play out in the wild will be crucial to incorporating such a framework into management practices.
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| 31. |
- Cote, J, et al.
(author)
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Personality-dependent dispersal : characterization, ontogeny and consequences for spatially structured populations
- 2010
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In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 365, s. 4065-4076
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Journal article (peer-reviewed)abstract
- Dispersal is one of the most fundamental components of ecology, and affects processes as diverse as population growth, metapopulation dynamics, gene flow and adaptation. Although the act of moving from one habitat to another entails major costs to the disperser, empirical and theoretical studies suggest that these costs can be reduced by having morphological, physiological or behavioural specializations for dispersal. A few recent studies on different systems showed that individuals exhibit personality-dependent dispersal, meaning that dispersal tendency is associated with boldness, sociability or aggressiveness. Indeed, in several species, dispersers not only develop behavioural differences at the onset of dispersal, but display these behavioural characteristics through their life cycle. While personality-dependent dispersal has been demonstrated in only a few species, we believe that it is a widespread phenomenon with important ecological consequences. Here, we review the evidence for behavioural differences between dispersers and residents, to what extent they constitute personalities. We also examine how a link between personality traits and dispersal behaviours can be produced and how personality-dependent dispersal affects the dynamics of metapopulations and biological invasions. Finally, we suggest future research directions for population biologists, behavioural ecologists and conservation biologists such as how the direction and the strength of the relationship between personality traits and dispersal vary with ecological contexts.
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- Dyberg, C., et al.
(author)
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Rho-associated kinase is a therapeutic target in neuroblastoma
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:32
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Journal article (peer-reviewed)abstract
- Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK) 2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3 beta-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.
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- Hao, Xiaojin, et al.
(author)
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Angiogenic effects of sequential release of VEGF-A(165) and PDGF-BB with alginate hydrogels after myocardial infarction
- 2007
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In: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 28, s. 612-612
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Journal article (peer-reviewed)abstract
- Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A(165) (VEGF-A(165)) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with I-125-labelled VEGF-A(165) and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A(165), PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gets were capable of delivering VEGF-A(165) and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A(165). Sequential growth factor administration led to a higher density of alpha-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A(165) and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.
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| 46. |
- Klaminder, Jonatan, et al.
(author)
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Long-Term Persistence of an Anxiolytic Drug (Oxazepam) in a Large Freshwater Lake
- 2015
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:17, s. 10406-10412
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Journal article (peer-reviewed)abstract
- Production and human consumption of pharmaceuticals result in contamination of surface waters worldwide. Little is known about the long-term (i.e., over decades) fate of pharmaceuticals in aquatic systems. Here, we show that the most prescribed anxiolytic in Sweden (oxazepam) persists in its therapeutic form for several decades after being deposited in a large freshwater lake. By comparing sediment cores collected in 1995 and 2013, we demonstrate that oxazepam inputs from the early 1970s remained in the sediments until sampling in 2013, despite in situ degradation processes and sediment diagenesis. In laboratory and pond experiments, we further reveal that therapeutic forms of oxazepam can persist over several months in cold (5 degrees C) lake water free from UV light. We conclude that oxazepam can persist in lakes over a time scale much longer than previously realized and that levels can build up in lakes due to both a legacy of past inputs and a growing urban population.
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| 47. |
- Lennox, Robert J., et al.
(author)
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A role for lakes in revealing the nature of animal movement using high dimensional telemetry systems
- 2021
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In: Movement Ecology. - : BioMed Central. - 2051-3933. ; 9:1
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Research review (peer-reviewed)abstract
- Movement ecology is increasingly relying on experimental approaches and hypothesis testing to reveal how, when, where, why, and which animals move. Movement of megafauna is inherently interesting but many of the fundamental questions of movement ecology can be efficiently tested in study systems with high degrees of control. Lakes can be seen as microcosms for studying ecological processes and the use of high-resolution positioning systems to triangulate exact coordinates of fish, along with sensors that relay information about depth, temperature, acceleration, predation, and more, can be used to answer some of movement ecology's most pressing questions. We describe how key questions in animal movement have been approached and how experiments can be designed to gather information about movement processes to answer questions about the physiological, genetic, and environmental drivers of movement using lakes. We submit that whole lake telemetry studies have a key role to play not only in movement ecology but more broadly in biology as key scientific arenas for knowledge advancement. New hardware for tracking aquatic animals and statistical tools for understanding the processes underlying detection data will continue to advance the potential for revealing the paradigms that govern movement and biological phenomena not just within lakes but in other realms spanning lands and oceans.
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| 48. |
- Lennox, Robert J., et al.
(author)
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Electronic tagging and tracking aquatic animals to understand a world increasingly shaped by a changing climate and extreme weather events
- 2024
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In: Canadian Journal of Fisheries and Aquatic Sciences. - 0706-652X .- 1205-7533. ; 81:3, s. 326-339
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Journal article (peer-reviewed)abstract
- Despite great promise for understanding the impacts and extent of climate change and extreme weather events on aquatic animals, their species, and ecological communities, it is surprising that electronic tagging and tracking tools, like biotelemetry and biologging, have not been extensively used to understand climate change or develop and evaluate potential interventions that may help adapt to its impacts. In this review, we provide an overview of methodologies and study designs that leverage available electronic tracking tools to investigate aspects of climate change and extreme weather events in aquatic ecosystems. Key interventions to protect aquatic life from the impacts of climate change, including habitat restoration, protected areas, conservation translocations, mitigations against interactive effects of climate change, and simulation of future scenarios, can all be greatly facilitated by using electronic tagging and tracking. We anticipate that adopting animal tracking to identify phenotypes, species, or ecosystems that are vulnerable or resilient to climate change will help in applying management interventions such as fisheries management, habitat restoration, invasive species control, or enhancement measures that prevent extinction and strengthen the resilience of communities against the most damaging effects of climate change. Given the scalability and increasing accessibility of animal tracking tools for researchers, tracking individual organisms will hopefully also facilitate research into effective solutions and interventions against the most extreme and acute impacts on species, populations, and ecosystems.
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| 49. |
- Lennox, Robert J., et al.
(author)
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Positioning aquatic animals with acoustic transmitters
- 2023
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In: Methods in Ecology and Evolution. - 2041-210X. ; 14:10, s. 2514-2530
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Research review (peer-reviewed)abstract
- Geolocating aquatic animals with acoustic tags has been ongoing for decades, relying on the detection of acoustic signals at multiple receivers with known positions to calculate a 2D or 3D position, and ultimately recreate the path of an aquatic animal from detections at fixed stations.This method of underwater geolocation is evolving with new software and hardware options available to help investigators design studies and calculate positions using solvers based predominantly on time-difference-of-arrival and time-of-arrival.We provide an overview of the considerations necessary to implement positioning in aquatic acoustic telemetry studies, including how to design arrays of receivers, test performance, synchronize receiver clocks and calculate positions from the detection data. We additionally present some common positioning algorithms, including both the free open-source solvers and the ‘black-box’ methods provided by some manufacturers for calculating positions.This paper is the first to provide a comprehensive overview of methods and considerations for designing and implementing better positioning studies that will support users, and encourage further knowledge advances in aquatic systems.
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| 50. |
- Lundin, Joakim, 1978-, et al.
(author)
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Analysis of four-wave mixing of high-power lasers for the detection of elastic photon-photon scattering
- 2006
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In: Physical Review A. Atomic, Molecular, and Optical Physics. - : The American Physical Society. - 1050-2947 .- 1094-1622. ; 74:4, s. 043821-043831
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Journal article (peer-reviewed)abstract
- We derive expressions for the coupling coefficients for electromagnetic four-wave mixing in the nonlinear quantum vacuum. An experimental setup for detection of elastic photon-photon scattering is suggested, where three incoming laser pulses collide and generate a fourth wave with a new frequency and direction of propagation. An expression for the number of scattered photons is derived and, using beam parameters for the Astra Gemini system at the Rutherford Appleton Laboratory, it is found that the signal can reach detectable levels. Problems with shot-to-shot reproducibility are reviewed, and the magnitude of the noise arising from competing scattering processes is estimated. It is found that detection of elastic photon-photon scattering may be achieved.
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