| 21. |
- Suomalainen, Anu, et al.
(författare)
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FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study.
- 2011
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Ingår i: Lancet neurology. - 1474-4465. ; 10:9, s. 806-818
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack of sensitive biomarkers in serum. Fibroblast growth factor 21 (FGF-21) is a growth factor with regulatory roles in lipid metabolism and the starvation response, and concentrations are raised in skeletal muscle and serum in mice with mitochondrial respiratory chain deficiencies. We investigated in a retrospective diagnostic study whether FGF-21 could be a biomarker for human mitochondrial disorders. METHODS: We assessed samples from adults and children with mitochondrial disorders or non-mitochondrial neurological disorders (disease controls) from seven study centres in Europe and the USA, and recruited healthy volunteers (healthy controls), matched for age where possible, from the same centres. We used ELISA to measure FGF-21 concentrations in serum or plasma samples (abnormal values were defined as >200 pg/mL). We compared these concentrations with values for lactate, pyruvate, lactate-to-pyruvate ratio, and creatine kinase in serum or plasma and calculated sensitivity, specificity, and positive and negative predictive values for all biomarkers. FINDINGS: We analysed serum or plasma from 67 patients (41 adults and 26 children) with mitochondrial disorders, 34 disease controls (22 adults and 12 children), and 74 healthy controls. Mean FGF-21 concentrations in serum were 820 (SD 1151) pg/mL in adult and 1983 (1550) pg/mL in child patients with respiratory chain deficiencies and 76 (58) pg/mL in healthy controls. FGF-21 concentrations were high in patients with mitochondrial disorders affecting skeletal muscle but not in disease controls, including those with dystrophies. In patients with abnormal FGF-21 concentrations in serum, the odds ratio of having a muscle-manifesting mitochondrial disease was 132·0 (95% CI 38·7-450·3). For the identification of muscle-manifesting mitochondrial disease, the sensitivity was 92·3% (95% CI 81·5-97·9%) and specificity was 91·7% (84·8-96·1%). The positive and negative predictive values for FGF-21 were 84·2% (95% CI 72·1-92·5%) and 96·1 (90·4-98·9%). The accuracy of FGF-21 to correctly identify muscle-manifesting respiratory chain disorders was better than that for all conventional biomarkers. The area under the receiver-operating-characteristic curve for FGF-21 was 0·95; by comparison, the values for other biomarkers were 0·83 lactate (p=0·037, 0·83 for pyruvate (p=0·015), 0·72 for the lactate-to-pyruvate ratio (p=0·0002), and 0·77 for creatine kinase (p=0·013). INTERPRETATION: Measurement of FGF-21 concentrations in serum identified primary muscle-manifesting respiratory chain deficiencies in adults and children and might be feasible as a first-line diagnostic test for these disorders to reduce the need for muscle biopsy. FUNDING: Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Molecular Medicine Institute of Finland, University of Helsinki, Helsinki University Central Hospital, Academy of Finland, Novo Nordisk, Arvo and Lea Ylppö Foundation.
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| 22. |
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| 23. |
- Yan, C., et al.
(författare)
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Size-dependent influence of NOx on the growth rates of organic aerosol particles
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:22
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.
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| 24. |
- Ahlm, Lars, et al.
(författare)
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Modeling the thermodynamics and kinetics of sulfuric acid-dimethylamine-water nanoparticle growth in the CLOUD chamber
- 2016
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 50:10, s. 1017-1032
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Tidskriftsartikel (refereegranskat)abstract
- Dimethylamine (DMA) has a stabilizing effect on sulfuric acid (SA) clusters, and the SA and DMA molecules and clusters likely play important roles in both aerosol particle formation and growth in the atmosphere. We use the monodisperse particle growth model for acid-base chemistry in nanoparticle growth (MABNAG) together with direct and indirect observations from the CLOUD4 and CLOUD7 experiments in the cosmics leaving outdoor droplets (CLOUD) chamber at CERN to investigate the size and composition evolution of freshly formed particles consisting of SA, DMA, and water as they grow to 20nm in dry diameter. Hygroscopic growth factors are measured using a nano-hygroscopicity tandem differential mobility analyzer (nano-HTDMA), which combined with simulations of particle water uptake using the thermodynamic extended-aerosol inorganics model (E-AIM) constrain the chemical composition. MABNAG predicts a particle-phase ratio between DMA and SA molecules of 1.1-1.3 for a 2nm particle and DMA gas-phase mixing ratios between 3.5 and 80 pptv. These ratios agree well with observations by an atmospheric-pressure interface time-of-flight (APi-TOF) mass spectrometer. Simulations with MABNAG, direct observations of the composition of clusters <2nm, and indirect observations of the particle composition indicate that the acidity of the nucleated particles decreases as they grow from approximate to 1 to 20nm. However, MABNAG predicts less acidic particles than suggested by the indirect estimates at 10nm diameter using the nano-HTDMA measurements, and less acidic particles than observed by a thermal desorption chemical ionization mass spectrometer (TDCIMS) at 10-30nm. Possible explanations for these discrepancies are discussed.
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| 25. |
- Allen, Naomi E, et al.
(författare)
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Selenium and Prostate Cancer : Analysis of Individual Participant Data From Fifteen Prospective Studies.
- 2016
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 108:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.
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| 26. |
- Almeida, Joao, et al.
(författare)
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Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
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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.
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| 27. |
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| 28. |
- Bondia-Pons, Isabel, et al.
(författare)
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Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight : a Big Mac challenge
- 2014
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 28:9, s. 4169-4179
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Tidskriftsartikel (refereegranskat)abstract
- Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m(2)). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels.
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| 29. |
- Brönnimann, D., et al.
(författare)
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The lay of land: Strontium isotope variability in the dietary catchment of the Late Iron Age proto-urban settlement of Basel-Gasfabrik, Switzerland
- 2018
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Ingår i: Journal of Archaeological Science: Reports. - : Elsevier BV. - 2352-409X. ; 17, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- Basel-Gasfabrik (Switzerland) comprises an extensive La Tène (chiefly Lt D, 150–80 BCE) settlement and two associated cemeteries at which strontium (87Sr/86Sr) isotope analysis of human and animal teeth investigated regional and supra-regional contacts. The interpretation of the analytic data, however, requires information on the isotopic baseline values around the site. Using 102 modern vegetation and 9 water samples from 51 localities, this study characterizes the isotopic ratios of the biologically available strontium of geological units and watercourses around Basel and compares these to 28 human infant, 6 pig, and 5 dog teeth from the site. Furthermore, pedological criteria evaluate the suitability of landforms for crop and pasturelands. The 87Sr/86Sr ratios of the environmental samples from geological units in up to 50 km distance varied between 0.70776 and 0.71794. Human infant teeth exhibited much more homogeneous 87Sr/86Sr ratios (0.70847–0.70950), which coincided largely with those of potential arable soils around Basel and indicate targeted exploitation of landscapes for agriculture. The more variable values of the faunal teeth suggest more widely ranging habitats or imports from the site's hinterlands. Two local isotope ranges were defined based on archaeological enamel samples and modern vegetation data from a confined radius around Basel. The study documents the complexity of distinguishing local and non-local individuals in a geologically heterogeneous region as well as the potential of isotope analyses to explore prehistoric land-use patterns.
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| 30. |
- Geng, Q., et al.
(författare)
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Temperature limit values for touching cold surfaces with the fingertip
- 2006
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 50:8, s. 851-862
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: At the request of the European Commission and in the framework of the European Machinery Directive, research was performed in five different laboratories to develop specifications for surface temperature limit values for the short-term accidental touching of the fingertip with cold surfaces. Methods: Data were collected in four laboratories with a total of 20 males and 20 females performing a grand total of 1655 exposures. Each touched polished blocks of aluminium, stainless steel, nylon-6 and wood using the distal phalanx of the index finger with a contact force of 1.0, 2.9 and 9.8 N, at surface temperatures from +2 to -40 degrees C for a maximum duration of 120 s. Conditions were selected in order to elicit varying rates of skin cooling upon contact. Contact temperature (T-C) of the fingertip was measured over time using a T-type thermocouple. Results: A database obtained from the experiments was collated and analysed to characterize fingertip contact cooling across a range of materials and surface temperatures. The database was subsequently used to develop a predictive model to describe the contact duration required for skin contact temperature to reach the physiological criteria of onset of pain (15 degrees C), onset of numbness (7 degrees C) and onset of frostbite risk (0 degrees C). Conclusions: The data reflect the strong link between the risk of skin damage and the thermal properties of the material touched. For aluminium and steel, skin temperatures of 0 degrees C occurs within 2-6 s at surface temperatures of -15 degrees C. For non-metallic surfaces, onset of numbness occurs within 15-65 s of contact at -35 degrees C and onset of cold pain occurs within 5 s of contact at -20 degrees C. The predictive model subsequently developed was a non-linear exponential expression also reflecting the effects of material thermal properties and initial temperature. This model provides information for the protection of workers against the risk of cold injury by establishing the temperature limits of cold touchable surfaces for a broad range of materials, and it is now proposed as guidance values in a new international standard.
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