| 1. |
- Kulmala, Markku, et al.
(författare)
-
Direct Observations of Atmospheric Aerosol Nucleation
- 2013
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6122, s. 943-946
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric nucleation is the dominant source of aerosol particles in the global atmosphere and an important player in aerosol climatic effects. The key steps of this process occur in the sub-2-nanometer (nm) size range, in which direct size-segregated observations have not been possible until very recently. Here, we present detailed observations of atmospheric nanoparticles and clusters down to 1-nm mobility diameter. We identified three separate size regimes below 2-nm diameter that build up a physically, chemically, and dynamically consistent framework on atmospheric nucleation-more specifically, aerosol formation via neutral pathways. Our findings emphasize the important role of organic compounds in atmospheric aerosol formation, subsequent aerosol growth, radiative forcing and associated feedbacks between biogenic emissions, clouds, and climate.
|
|
| 2. |
- Nummela, Aleksi, et al.
(författare)
-
Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine : a randomised controlled trial using tandem mass spectrometry
- 2022
-
Ingår i: BJA Open. - : Elsevier. - 2772-6096. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThis exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection.MethodsIn this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (n=160) received equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml−1; n=40), propofol (1.7 μg ml−1; n=40), sevoflurane (0.9% end-tidal; n=40), S-ketamine (0.75 μg ml−1; n=20), or placebo (n=20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed.ResultsStatistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P-value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) –1.19 (–1.6; –0.78), P<0.001 and 12,13-DiHOME –1.22 (–1.66; –0.77), P<0.001 were affected. Propofol elevated 9,10-DiHOME 2.29 (1.62; 2.96), P<0.001 and 12,13-DiHOME 2.13 (1.42; 2.84), P<0.001. Analytes were mostly unaffected by S-ketamine. Sevoflurane decreased tauroursodeoxycholic acid (TUDCA) –2.7 (–3.84; –1.55), P=0.015.ConclusionsDexmedetomidine-induced oxylipin alterations may be connected to pathways associated with organ protection. In contrast to dexmedetomidine, propofol emulsion elevated DiHOMEs, oxylipins associated with acute respiratory distress syndrome, and mitochondrial dysfunction in high concentrations. Further research is needed to establish the behaviour of DIHOMEs during prolonged propofol/dexmedetomidine infusions and to verify the sevoflurane-induced reduction in TUDCA, a suggested neuroprotective agent.Clinical trial registrationNCT02624401.
|
|
| 3. |
- Almeida, Joao, et al.
(författare)
-
Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
-
Tidskriftsartikel (refereegranskat)abstract
- Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
|
|
| 4. |
- Halonen, Jaana, et al.
(författare)
-
Psychotropic medication before and after disability retirement by pre-retirement perceived work-related stress
- 2020
-
Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 30:1, s. 158-163
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Retirement has been associated with improved mental health, but it is unclear how much this is due to the removal of work-related stressors. We examined rates of psychotropic medication use before and after the transition to disability retirement due to mental, musculoskeletal and other causes by pre-retirement levels of perceived work stress (effort-reward imbalance, ERI). Methods: Register-based date and diagnosis of disability retirement of 2766 participants of the Finnish Public Sector study cohort were linked to survey data on ERI, socialand health-related covariates, and to national records on prescribed reimbursed psychotropic medication, measured as defined daily doses (DDDs). Follow-up for DDDs was 2–5 years before and after disability retirement. We assessed differences in the levels of DDDs before and after retirement among those with high vs. low level of pre-retirement ERI with repeated measures regression. Results: Those with high (vs. low) levels of ERI used slightly more psychotropic medication before disability retirement due to mental disorders [rate ratio (RR) 1.14, 95% confidence intervals (CI) 0.94–1.37], but after retirement this difference attenuated (RR 0.94, 95% CI 0.80–1.10, P for interaction 0.02). Such a change was not observed for the other causes of disability retirement. Conclusions: The level of psychotropic medication use over the transition to disability retirement due to mental, but not musculoskeletal or other, causes was modified by pre-retirement perceived work-related stress. This suggests that among people retiring due to mental disorders those who had stressful jobs benefit from retirement more than those with low levels of work-related stress.
|
|
| 5. |
- Kantonen, Oskari, et al.
(författare)
-
Decreased thalamic activity is a correlate for disconnectedness during anesthesia with Propofol, Dexmedetomidine and Sevoflurane but not S-ketamine
- 2023
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 43:26, s. 4884-4895
-
Tidskriftsartikel (refereegranskat)abstract
- Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 μg/ml; n = 20), or saline placebo (n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMRglu) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness.
|
|
| 6. |
- Kantonen, Oskari, et al.
(författare)
-
Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine
- 2023
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 43:26, s. 4884-4895
-
Tidskriftsartikel (refereegranskat)abstract
- Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 μg/ml; n = 20), or saline placebo (n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMRglu) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness.
|
|
| 7. |
- Kirkby, Jasper, et al.
(författare)
-
Ion-induced nucleation of pure biogenic particles
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 521-526
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.
|
|
| 8. |
- Kulmala, Markku, et al.
(författare)
-
Measurement of the nucleation of atmospheric aerosol particles
- 2012
-
Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 7:9, s. 1651-1667
-
Tidskriftsartikel (refereegranskat)abstract
- The formation of new atmospheric aerosol particles and their subsequent growth have been observed frequently at various locations all over the world. The atmospheric nucleation rate (or formation rate) and growth rate (GR) are key parameters to characterize the phenomenon. Recent progress in measurement techniques enables us to measure atmospheric nucleation at the size (mobility diameter) of 1.5 (+/- 0.4) nm. The detection limit has decreased from 3 to 1 nm within the past 10 years. In this protocol, we describe the procedures for identifying new-particle-formation (NPF) events, and for determining the nucleation, formation and growth rates during such events under atmospheric conditions. We describe the present instrumentation, best practices and other tools used to investigate atmospheric nucleation and NPF at a certain mobility diameter (1.5, 2.0 or 3.0 nm). The key instruments comprise devices capable of measuring the number concentration of the formed nanoparticles and their size, such as a suite of modern condensation particle counters (CPCs) and air ion spectrometers, and devices for characterizing the pre-existing particle number concentration distribution, such as a differential mobility particle sizer (DMPS). We also discuss the reliability of the methods used and requirements for proper measurements and data analysis. The time scale for realizing this procedure is 1 year.
|
|
| 9. |
- Kulmala, Markku, et al.
(författare)
-
Overview of the biosphere-aerosol-cloud-climate interactions (BACCI) studies
- 2008
-
Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 60:3, s. 300-317
-
Forskningsöversikt (refereegranskat)abstract
- Here we present research methods and results obtained by the Nordic Centre of Excellence Biosphere-Aerosol-Cloud-Climate Interactions (BACCI) between 1 January 2003 and 31 December 2007. The centre formed an integrated attempt to understand multiple, but interlinked, biosphere-atmosphere interactions applying inter and multidisciplinary approaches in a coherent manner. The main objective was to study the life cycle of aerosol particles and their importance on climate change. The foundation in BACCI was a thorough understanding of physical, meteorological, chemical and ecophysiological processes, providing a unique possibility to study biosphere-aerosol-cloud-climate interactions. Continuous measurements of atmospheric concentrations and fluxes of aerosol particles and precursors and, CO2/aerosol trace gas interactions in different field stations (e.g. SMEAR) were supported by models of particle thermodynamics, transport and dynamics, atmospheric chemistry, boundary layer meteorology and forest growth. The main progress was related to atmospheric new particle formation, existence of clusters, composition of nucleation mode aerosol particles, chemical precursors of fresh aerosol particles, the contribution of biogenic aerosol particles on the global aerosol load, transport, transformation and deposition of aerosol particles, thermodynamics related to aerosol particles and cloud droplets, and the microphysics and chemistry of cloud droplet formation.
|
|
| 10. |
- Laaksonen, Reijo, et al.
(författare)
-
A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle
- 2006
-
Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects.METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg), atorvastatin (40 mg), or placebo.PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05), while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1) in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein.CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.
|
|
