| 1. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 2. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 3. |
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| 4. |
- Bennell, Kim L., et al.
(författare)
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Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol
- 2011
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people, giving rise to pain and loss of function. Many people experience progressive worsening of the disease over time, particularly those with varus malalignment and increased medial knee joint load. Therefore, interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression. Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load. A neuromuscular exercise program, emphasising optimal alignment of the trunk and lower limb joints relative to one another, as well as quality of movement performance, while dynamically and functionally strengthening the lower limb muscles, may be able to reduce medial knee load. Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature. This randomised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading, pain and function in individuals with medial knee joint osteoarthritis. We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program. Methods/Design: 100 people with medial knee pain, radiographic medial compartment osteoarthritis and varus malalignment will be recruited and randomly allocated to one of two 12-week exercise programs: quadriceps strengthening or neuromuscular exercise. Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home. The primary outcomes are medial knee load during walking (the peak external knee adduction moment from 3D gait analysis), pain, and self-reported physical function measured at baseline and immediately following the program. Secondary outcomes include the external knee adduction moment angular impulse, electromyographic muscle activation patterns, knee and hip muscle strength, balance, functional ability, and quality-of-life. Discussion: The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load, pain and physical function in people with medial knee osteoarthritis and varus malalignment.
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| 5. |
- Bennell, Kim L., et al.
(författare)
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Neuromuscular Versus Quadriceps Strengthening Exercise in Patients With Medial Knee Osteoarthritis and Varus Malalignment
- 2014
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191. ; 66:4, s. 950-959
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare the effects of neuromuscular exercise (NEXA) and quadriceps strengthening (QS) on the knee adduction moment (an indicator of medio-lateral distribution of knee load), pain, and physical function in patients with medial knee joint osteoarthritis (OA) and varus malalignment. Methods. One hundred patients with medial knee pain, mostly moderate-to-severe radiographic medial knee OA, and varus malalignment were randomly allocated to one of two 12-week exercise programs. Each program involved 14 individually supervised exercise sessions with a physiotherapist plus a home exercise component. Primary outcomes were peak external knee adduction moment (3-dimensional gait analysis), pain (visual analog scale), and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index). Results. Eighty-two patients (38 [76%] of 50 in the NEXA group and 44 [88%] of 50 in the QS group) completed the trial. There was no significant between-group difference in the change in the peak knee adduction moment (mean difference 0.13 Nm/[body weight x height]% [95% confidence interval (95% CI) -0.08, 0.33]), pain (mean difference 2.4 mm [95% CI -6.0, 10.8]), or physical function (mean difference -0.8 units [95% CI -4.0, 2.4]). Neither group showed a change in knee moments following exercise, whereas both groups showed similar significant reductions in pain and improvement in physical function. Conclusion. Although comparable improvements in clinical outcomes were observed with both neuromuscular and quadriceps strengthening exercise in patients with moderate varus malalignment and mostly moderate-to-severe medial knee OA, these forms of exercise did not affect the knee adduction moment, a key predictor of structural disease progression.
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| 6. |
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| 7. |
- Ehrhardt, Carsten, et al.
(författare)
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Current Progress Toward a Better Understanding of Drug Disposition Within the Lungs : Summary Proceedings of the First Workshop on Drug Transporters in the Lungs
- 2017
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 106:9, s. 2234-2244
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Tidskriftsartikel (refereegranskat)abstract
- The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin hosted the "1st Workshop on Drug Transporters in the Lungs" in September 2016 to discuss the impact of transporters on pulmonary drug disposition and their roles as drug targets in lung disease. The workshop brought together about 30 scientists from academia and pharmaceutical industry from Europe and Japan and addressed the primary questions: What do we know today, and what do we need to know tomorrow about transporters in the lung? The 3 themes of the workshop were: (1) techniques to study drug transporter expression and actions in the lungs; (2) drug transporter effects on pulmonary pharmacokinetics-case studies; and (3) transporters as drug targets in lung disease. Some of the conclusions of the workshop were: suitable experimental models that allow studies of transporter effects are available; data from these models convincingly show a contribution of both uptake and efflux transporters on pulmonary drug disposition; the effects of transporters on drug lung PK is now better conceptualized; some transporters are associated with lung diseases. However, more work is needed to establish which of the available models best translate to the clinical situation.
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| 8. |
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| 9. |
- Eriksson, Johanna, 1991-
(författare)
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Drug absorption in the lungs : studies in the isolated perfused rat lung model combined with physiologically based biopharmaceutics modelling
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary delivery of drugs is the preferred route of administration for treatment of local lung diseases like asthma and chronic obstructive pulmonary disease. Recently, there has also been increased interest in systemic delivery of drugs via the lungs to avoid problems with low and/or variable gastrointestinal absorption, and as a needle-free alternative for drugs that cannot be ingested. Both the pharmacological and the potentially adverse effects of inhaled drugs depend on the drug’s local and systemic concentrations, which in turn depend on the pulmonary absorption of the drug. Pulmonary drug absorption is governed by the dissolution, permeability, tissue retention, and non-absorptive clearance of the drug in the lungs. Predicting systemic and local exposure is necessary for developing an inhaled drug product, and these predictions can be based on data obtained from both in vitro and ex vivo methods, such as cell lines, solubility measurements, and the isolated perfused lung (IPL) model. Data obtained by these methods can then be used to inform physiologically based biopharmaceutics (PBB) models about drug-specific absorption parameters.The overall aim of this thesis was to increase the mechanistic understanding of pulmonary drug absorption, with a special focus on obtaining and analyzing ex vivo absorption parameters for different inhalation drugs and formulations, and evaluating the predictive power of these parameters in simulations of pulmonary drug absorption. In the first two papers of the thesis, drugs were formulated as solutions, suspensions, and dry powders, and pulmonary absorption of these were measured using the IPL model. The data from these experiments were then analyzed to obtain absorption parameters for each drug using a PBB model. Tissue retention was shown to be an important parameter for describing drug absorption in IPL, and particle wetting was shown to greatly affect the absorption of dry powders. Permeability in IPL correlated well with intrinsic permeability measured in cell monolayers, suggesting that passive transcellular transport is the main transport mechanism in the lungs. In the second two papers, the absorption parameters obtained from IPL data were used to simulate rat and human pulmonary drug absorption. The simulations predicted systemic exposure after inhalation well for both rat and human, suggesting that ex vivo parameters can be used to predict rat in vivo and human plasma concentrations. This thesis deepens our understanding of absorption parameters involved in pulmonary drug absorption, and suggests applications for these parameters in predictions of local and systemic exposure after inhalation.
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| 10. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 11. |
- Kumar, Abhinav, et al.
(författare)
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A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.
- 2017
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 34:12, s. 2454-2465
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.METHODS: The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.RESULTS: SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.CONCLUSION: The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.
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| 12. |
- Kumar, Abhinav, et al.
(författare)
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Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans
- 2017
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Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 13:8, s. 2517-2521
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Tidskriftsartikel (refereegranskat)abstract
- Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of α1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.
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| 13. |
- Kumar, Abhinav, et al.
(författare)
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Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid
- 2016
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Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 12:4, s. 1033-1043
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Tidskriftsartikel (refereegranskat)abstract
- When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.
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| 14. |
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| 15. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 16. |
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| 17. |
- Selley, Liza, et al.
(författare)
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Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages
- 2020
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Ingår i: Metallomics. - : Royal Society of Chemistry. - 1756-5901 .- 1756-591X. ; 12:3, s. 371-386
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Tidskriftsartikel (refereegranskat)abstract
- Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4–25 μg ml−1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
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| 18. |
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