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Funding Information: We acknowledge all the participants and researchers of the 23 biobanks that have contributed to the GBMI. Biobank-specific acknowledgments are included in the Data S3 . We thank H. Huang, A.R. Martin, B.M. Neale, Y. Okada, K. Tsuo, J.C. Ulirsch, Y. Wang, and all the members of Finucane and Daly labs for their helpful feedback. M.K. was supported by a Nakajima Foundation Fellowship and the Masason Foundation . H.K.F. was funded by NIH grant DP5 OD024582 . Publisher Copyright: © 2022 The Author(s) Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWASs). Fine-mapping of meta-analysis studies is typically performed as in a single-cohort study. Here, we first demonstrate that heterogeneity (e.g., of sample size, phenotyping, imputation) hurts calibration of meta-analysis fine-mapping. We propose a summary statistics-based quality-control (QC) method, suspicious loci analysis of meta-analysis summary statistics (SLALOM), that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics. We validate SLALOM in simulations and the GWAS Catalog. Applying SLALOM to 14 meta-analyses from the Global Biobank Meta-analysis Initiative (GBMI), we find that 67% of loci show suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci are significantly depleted for having nonsynonymous variants as lead variant (2.7×; Fisher's exact p = 7.3 × 10−4). We find limited evidence of fine-mapping improvement in the GBMI meta-analyses compared with individual biobanks. We urge extreme caution when interpreting fine-mapping results from meta-analysis of heterogeneous cohorts.

Lung function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry GWAS meta-analysis of lung function to date, comprising 580,869 participants, 1020 independent association signals identified 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score (GRS) showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies (PheWAS) for selected associated variants, and trait and pathway-specific GRS to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Background: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone.Research Question: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma?Study Design and Methods: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10–6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2).Results: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10–8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent.Interpretation: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.

BACKGROUND: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown. OBJECTIVE: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile. DESIGN: Randomised, open-label, controlled, parallel group, phase IV clinical drug trial. SETTING: The study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017. PARTICIPANTS: One hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable. INTERVENTIONS: Volunteers were randomised to receive a 1-h exposure to 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 = 39), S-ketamine (0.75 μg ml-1; n = 20) or placebo (n = 20). MAIN OUTCOME MEASURES: Metabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min postanaesthesia. RESULTS: All metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereas branched chain amino acids and tyrosine decreased. CONCLUSION: A 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror α2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624401. URL: https://clinicaltrials.gov/ct2/show/NCT02624401. CC BY 4.0September 15, 2021Correspondence to Aleksi J. Nummela, Department of Internal Medicine, Turku University Hospital, 20521 Turku, Finland E-mail: aljunu@utu.fiFinancial support and sponsorship: this work was supported by Academy of Finland, Helsinki, Finland (grant numbers 266467, 266434); Jane and Aatos Erkko Foundation, Helsinki, Finland; The Finnish Medical Foundation, Helsinki, Finland (JWL); The Emil Aaltonen Foundation, Tampere, Finland (JWL); and The Paulo Foundation, Espoo, Finland (LTL) and Orion Research Foundation, Espoo, Finland (LTL); Signe and Ane Gyllenberg Foundation, Helsinki, Finland (KJV); The Finnish Medical Foundation, Eero Matti Raninen Fund, Helsinki, Finland (AJN) and University of Turku, Finland (AJN).

Funding Information: The work of the contributing biobanks was supported by numerous grants from governmental and charitable bodies. Biobank-specific acknowledgments and more detailed acknowledgments are included in Data S2. Initiative management, S.B.C. J.C. N.J.C. M.J.D. E.E.K. A.R.M. B.M.N. Y.O. A.V.P. D.A.v.H. R.G.W. C.J.W. W.Z. and S.Z.; individual biobank analysis, A.B. Y.B. B.M.B. C.D.B. S.C. T.-T.C. K.C. S.M.D. M.D. G.H.d.B. Y.D. N.J.D. M.-J.F. Y.-C.A.F. S.F. V.L.F. L.G.F. E.R.G. T.R.G. D.H.G. C.R.G. G.G.-A. S.E.G. L.A.G. C.H. J.B.H. W.E.H. H.H. K.H. N.I. A.I. R.J. M. Kurki, J.K. N.K. E.E.K. J.T.K. M. Kanai, T.L. K.L. M.H.L. S.L. K.L. Y.-F.L. V.L.F. R.J.F.L. E.A.L.-M. A.R.-M. S.M.-G. R.M. R.E.M. H.C.M. A.R.M. Y.M. H.M. S.E.M. I.Y.M. B.M. S.M. K.N. S.N. M.A.N.-A. K.N. Y.O. P.P. A.L.-P. A.P. B.P. S.P. M.H.P. D.J.R. N.R. M.D.R. A.R. C.S. S.S. S.S.S. J.A.S. P.S. I.S. T.T. R.T. K.T. J.U. D.A.v.H. B.V. M.V. Y.V. J.M.V. R.G.W. Y.W. S.J.W. B.N.W. K.-H.H.W. M.Z. X.Z. and S.Z.; individual biobank management, N.A. A.A.T. K.M.A.-D. P.A. K.C.B. M. Boehnke, M. Boezen, C.D.B. A.C. Z.C. C.-Y.C. J.C. N.J.C. S.M.D. S.F. Y.-C.A.F. S.F. E.F. T.G. C.R.G. C.J.G. Y.G. H.H. K.A.H. K.H. S.I.I. N.M.J. N.K. E.E.K. J.T.K. C.L. M.H.L. M.T.M.L. L.L. K.L. Y.-F.L. R.J.F.L. J.L. S.M. Y.M. K.M. I.Y.M. Y.O. C.M.O. A.V.P. B.P. D.J.P. D.J.R. M.D.R. S.S. J.W.S. H.S. K.S. T.T. U.T. R.C.T. D.A.v.H. M.V. R.G.W. D.C.W. C.W. J.W. M.Z. X.Z. and S.Z.; study design and interpretation of results, A.B. M. Boehnke, M. Boezen, B.M.B. T.-T.C. C.-Y.C. M.J.D. G.D.S. N.J.D. S.F. M.-J.F. H.K.F. E.R.G. A.G. T.G. J.B.H. J.H. K.H. R.J. M.K. E.E.K. T.K. C.M.L. V.L.F. E.A.L.-M. A.R.M. S.N. B.M.N. C.M.O. J.J.P. B.P. N.R. H.R. J.A.S. I.S. K.T. D.A.v.H. R.G.W. Y.W. D.C.W. S.J.W. C.J.W. B.N.W. J.W. K.-H.H.W. M.Z. H.Z. J.Z. W.Z. X.Z. and S.Z.; drafted and edited the paper, A.B. M. Boehnke, M. Boezen, M.J.D. G.H.d.B. N.J.D. T.R.G. J.B.H. N.I. N.M.J. M.K. V.L.F. S.M. A.R.M. H.M. S.N. B.M.N. C.M.O. B.P. H.R. C.S. J.A.S. J.W.S. K.T. Y.W. D.C.W. C.J.W. K.-H.H.W. H.Z. J.Z. W.Z. and S.Z.; primary meta-analysis and quality control, M.J.D. H.K.F. M. Kanai, J.K. J.T.K. M. Kurki, M.M. B.M.N. C.J.W. K.-H.H.W. and W.Z.; drug discovery: S.N. T.K. K.-H.H.W. W.Z. and Y.O.; fine mapping, M. Kanai, W.Z. M.J.D. and H.K.F.; polygenic risk score, Y.W. S.N. E.A.L.-M. S.K. K.T. K.L. M. Kanai, W.Z. K.W. M.-J.F. L.B. P.A. P.D. V.L.F. R.M. Y.M. B.B. S.S. J.U. E.R.G. N.J.C. I.S. Y.O. A.R.M. and J.B.H.; proteome-wide Mendelian randomization, H.Z. H.R. A.B. G.H. G.D.S. B.M.B. W.Z. B.M.N. T.R.G. and J.Z.; transcriptome-wide association study, A.B. J.B.H. W.Z. J.Z. M. Kanai, B.P. E.R.G. and N.J.C.; asthma, K.T. W.Z. Y.W. M. Kanai, S.N. Y.O. B.M.N. M.J.D. and A.R.M.; heart failure, K.-H.H.W. N.J.D. B.N.W. I.S. S.E.G. J.B.H. N.J.C. M.P. R.J.F.L. M.J.D. B.M.N. W.Z. W.E.H. and C.J.W.; idiopathic pulmonary fibrosis, J.J.P. W.Z. M.J.D. J.T.K. N.J.C. and J.B.H.; primary open-angle glaucoma, V.L.F. A.B. W.Z. Y.W. K.L. M. Kanai, E.A.L.-M. P.S. R.T. X.Z. S.N. S.S. Y.O. N.I. S.M. H.S. I.S. C.W. A.R.M. E.R.G. N.M.J. N.J.C. and J.B.H.; stroke, I.S. K.-H.H.W. W.H. B.N.W. W.Z. J.E.H. A.P. B.B. A.H.S. M.E.G. R.G.W. K.H. C.K. S.Z. M.J.D. B.M.N. and C.J.W.; venous thromboembolism, B.N.W. I.S. K.-H.H.W. B.B. V.L.F. K.T. M.D. B.N. W.Z. J.A.S. and C.J.W. All authors reviewed the manuscript. M.J.D. is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and a consultant for Camp4 Therapeutics, Takeda Pharmaceutical, and Biogen. The spouse of C.J.W. works at Regeneron Pharmaceuticals. C.-Y.C. is employed by Biogen. C.R.G. owns stock in 23andMe, Inc. T.R.G. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. E.E.K. has received speaker fees from Regeneron, Illumina, and 23andMe and is a member of the advisory board for Galateo Bio. R.E.M. has received speaker fees from Illumina and is a scientific advisor to the Epigenetic Clock Development Foundation. G.D.S. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. K.S. and U.T. are employed by deCODE Genetics/Amgen, Inc. J.Z. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. S.M. is a co-founder of and holds stock in Seonix Bio. Publisher Copyright: © 2022 Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.

Background This methodological paper describes the integration of the European Health Interview Survey wave 3 (EHIS 3) into the National FinSote Survey (FinSote2019/EHIS). Finnish Institute for Health and Welfare (THL) conducted the survey in Finland. Methods FinSote 2019/EHIS was conducted as a cross-sectional health, welfare and services survey. A simple random sampling was used to recruit 15 000 individuals aged 15 years and older. Data collection was carried out by self-administered questionnaire that was available in web and paper form. To minimize the respondent burden socio-demographic background variables were obtained from administrative registers. In Finland, EHIS wave 3 was conducted as a part of the National FinSote survey. The questionnaire included both EHIS 3 modules on health status, health care, health determinants (excluding derogation variables), social background variables and additional national questions. In data processing, two datasets were formed: national dataset for sustaining time series as well as monitoring nationally relevant topics and EHIS dataset including the quality and validation rules specified by Eurostat. Results In total, 6,251 questionnaires were completed. The response rate was 44 % in EHIS data (aged 15+) and 45 % in national FinSote data (aged 20+). The representativeness of the results was increased by applying weighting procedures. The sample size was just large enough to achieve the precision requirements determined by Eurostat. Access to micro data of the EHIS 3 will be provided by Eurostat and to the FinSote 2019/EHIS by THL. Conclusions Integrating EHIS wave 3 into an existing national monitoring system was challenging in Finland. The harmonization might lead to interruptions of existing national time trends. Inclusion of some national well-being and social care variables might be irrelevant to respondent aged 15-19 years. Key messages Conducting EHIS as a part of National FinSote survey in Finland was cost-effective but challenging. Cultural differences in regards to living conditions in younger respondents and health care system made it challenging to integrate EHIS into national survey.

Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases

Today, the near-Earth space is facing a paradigm change as the number of new spacecraft is literally sky-rocketing. Increasing numbers of small satellites threaten the sustainable use of space, as without removal, space debris will eventually make certain critical orbits unusable. A central factor affecting small spacecraft health and leading to debris is the radiation environment, which is unpredictable due to an incomplete understanding of the near-Earth radiation environment itself and its variability driven by the solar wind and outer magnetosphere. This paper presents the FORESAIL-1 nanosatellite mission, having two scientific and one technological objectives. The first scientific objective is to measure the energy and flux of energetic particle loss to the atmosphere with a representative energy and pitch angle resolution over a wide range of magnetic local times. To pave the way to novel model - in situ data comparisons, we also show preliminary results on precipitating electron fluxes obtained with the new global hybrid-Vlasov simulation Vlasiator. The second scientific objective of the FORESAIL-1 mission is to measure energetic neutral atoms (ENAs) of solar origin. The solar ENA flux has the potential to contribute importantly to the knowledge of solar eruption energy budget estimations. The technological objective is to demonstrate a satellite de-orbiting technology, and for the first time, make an orbit manoeuvre with a propellantless nanosatellite. FORESAIL-1 will demonstrate the potential for nanosatellites to make important scientific contributions as well as promote the sustainable utilisation of space by using a cost-efficient de-orbiting technology., Comment: 26 pages, 7 figures, 5 tables Published online in JGR: Space Physics on 21 May 2019

Modifications of the drift-kinetic transport code XGC0 to include the transport, ionization, and recombination of individual charge states, as well as the associated radiation, are described. The code is first applied to a simulation of an NSTX H-mode discharge with carbon impurity to demonstrate the approach to coronal equilibrium. The effects of neoclassical phenomena on the radiated power profile are examined sequentially through the activation of individual physics modules in the code. Orbit squeezing and the neoclassical inward pinch result in increased radiation for temperatures above a few hundred eV and changes to the ratios of charge state emissions at a given electron temperature. Analogous simulations with a neon impurity yield qualitatively similar results. Keywords: Neoclassical transport, Impurity radiation, Coronal equilibrium, Kinetic simulation, Particle-in-cell, Spherical torus

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Characterization of host and parasite population genetic structure and estimation of gene flow among populations are essential for the understanding of parasite local adaptation and coevolutionary interactions between hosts and parasites. We examined two aspects of population structure in a parasitic plant, the greater dodder (Cuscuta europaea) and its host plant, the stinging nettle (Urtica dioica), using allozyme data from 12 host and eight parasite populations. First, we examined whether hosts exposed to parasitism in the past contain higher levels of genetic variation. Second, we examined whether host and parasite populations differ in terms of population structure and if their population structures are correlated. There was no evidence that host populations differed in terms of gene diversity or heterozygosity according to their history of parasitism. Host populations were genetically more differentiated (F(ST) = 0.032) than parasite populations (F(ST) = 0.009). Based on these F(ST) values, gene flow was high for both host and parasite. Such high levels of gene flow could counteract selection for local adaptation of the parasite. We found no significant correlation between geographic and genetic distance (estimated as pairwise F(ST)), either for the host or for the parasite. Furthermore, host and parasite genetic distance matrices were uncorrelated, suggesting that sites with genetically similar host populations are unlikely to have genetically similar parasite populations.

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler® and Turbuhaler® for the delivery of budesonide 200 μg/dose twice daily in steroid-naı̈ve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-naı̈ve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 μg/day either via Easyhaler® (n = 159) or via Turbuhaler® (n = 167), plus salbutamol inhalation powder (100 μg/dose) via Easyhaler® as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler® group and 149 in the Turbuhaler® group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7–8. At weeks 7–8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from −8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler® more acceptable than Turbuhaler®. The results show that budesonide via Easyhaler® is clinically as effective as Pulmicort® Turbuhaler® when equal daily doses of budesonide are delivered to steroid-naı̈ve asthmatic patients. Moreover, patients found Easyhaler® more acceptable than Turbuhaler®, and a majority would prefer Easyhaler® if given a choice.

Crops growing at high latitudes are adapted to low intensities of solar ultraviolet B radiation (UV-B). As a result of destruction of stratospheric ozone layer especially at the Polar Regions of the globe, the intensity of UV-B is projected to increase at high latitudes. In order to find out the consequences of increased UV-B on crops, the sensitivity of different varieties of barley, wheat, oats, clover, timothy, meadow fescue, tall fescue and potato was tested in Jokioinen, Finland. The experiment was conducted in the field, under natural light, with a continuous 30 % increase in UV-B. Both increased UV-B and the control with slightly increased UV-A radiation affected the number of lateral shoots in cereals, and the specific leaf area and the content of phenolic substances in grasses. The effects varied according to plant variety and time of growing season. However, no visible damage, nor changes in biomass and yield production were found in any of the crops. Long-term effects on, e.g. genetic stability and germination of crop seed remain to be studied. Empfindlichkeit von Kulturpflanzenbestanden gegenuber einer Erhohung der ultravioletten Einstrahlung unter nordlichen Wachstumsbedingungen Kulturpflanzenbestande, die unter hohen Breitengraden wachsen, sind an geringe Intensitaten der solaren ultravioletten B Einstrahlung (UV-B) angepasst. Aufgrund der Destruktion der Stratosphare, insbesondere der Ozonschicht, im Bereich der polaren Gebiete der Erde, ist eine zunehmende Intensitat der UV-B Strahlung in hohen Breitengraden festzustellen. Um die Konsequenzen einer Erhohung von UV-B auf Kulturpflanzenbestande zu bestimmen, wurde die Empfindlichkeit unterschiedlicher Arten wie Gerste, Weizen, Hafer, Klee, Wiesenlieschgras, Wiesenschwingel, Rohrschwingel und Kartoffel in Jokioinen, Finnland, untersucht. Das Experiment wurde im Felde durchgefuhrt unter naturlichen Lichtbedingungen mit einer kontinuierlichen Zunahme von 30 % fur UV-B. Sowohl eine Erhohung der UV-B als auch die Kontrolle mit leicht erhohten UV-B Strahlungen beeinflussten die Anzahl der Nebenwurzeln bei den Getreidepflanzen und die spezifische Blattflache sowie den Gehalt an phenolischen Substanzen bei den Grasern. Die Wirkungen variierten entsprechend der Pflanzenvarietat und der Anbauzeit. Allerdings wurden keine erkennbare Schadigungen noch Anderungen in der Biomasse und in der Ertragsproduktion bei einer der untersuchten Pflanzenbestande gefunden. Langzeitwirkungen auf die genetische bedingte Stabilitat und Keimung der Kulturpflanzen sollte weiterhin untersucht werden.

Objective: The aim of this study was to compare the bronchodilating effect, tolerability and acceptability of a single 100μg dose of salbutamol inhaled via Easyhaler® multidose dry powder inhaler with a single 250μg dose of terbutaline inhaled via Turbuhaler®, also a multidose dry powder inhaler. Design, Setting and Patients: The study was conducted according to a single-dose, crossover, randomised, double-blind with double-dummy design in four centres in Finland. A total of 29 adult patients with stable asthma without previous experience with the tested devices completed the study, which comprised 2 study days with 4-hour follow-up periods including spirometric measurements. The acceptability of the devices to the patients in the study was also evaluated. Results: The mean (SD) maximum value of forced expiratory volume in 1 second (FEV1max) after salbutamol Easyhaler® was 3.14L (1.26L), and after terbutaline Turbuhaler® was 3.07L(1.11L). The mean (SD) percentage change from baseline of forced expiratory volume in 1 second (FEV1) to FEV1max was 12.7% (12.4%) after Easyhaler® and 13.1% (10.8%) after Turbuhaler®. The observed differences in the increase in FEV1 and in the area under the curve (AUC) of FEV1 between the treatments were not statistically significant. Four patients reported mild adverse events after inhaling salbutamol via Easyhaler®, compared with five patients who reported adverse events after inhaling terbutaline via Turbuhaler®. Based on the VAS assessment of the acceptability, Easyhaler® was found to be better accepted than Turbuhaler® in terms of ease of administration, ease of inhaling, and the strength of sensation on receiving a dose. Overall, 62% of the patients would have chosen Easyhaler®. Conclusions: Easyhaler® containing salbutamol (100μg/dose) is comparable in efficacy and as well tolerated as Turbuhaler® containing terbutaline (250μg/dose), and Easyhaler® was well accepted by patients.

This is a study on associations between the number of close friends and mental well-being in a nationwide sample of the Finnish general population (n = 1,603). Mental well-being was assessed by means of the 12-item General Health Questionnaire. A total of 3% of the sample had no close friends and another 3% had only one. Over half of the sample (52%) reported having five or more friends. The overall prevalence of mental distress was 15% in men and 21% in women. According to multivariate analyses the risk of mental distress was increased in men among those with no friends (odds ratio [OR]: 2.70) and among those who had one (OR: 4.32) or two to four friends (OR: 1.75), as compared with those who had more friends. In women, having only one friend (OR: 2.30), insufficient family support (OR: 1.63) and insufficient support from relatives (OR: 1.77) associated with the risk of mental distress. These results suggest that mental well-being might be promoted if mentally distressed men seeking professional help were supported in building up and maintaining social networks and mentally distressed women were supported in harmonizing their family life.

Following the installation of the ITER-like wall (ILW) at JET, carbon has been replaced by beryllium and tungsten as the main core plasma impurity. Simultaneously, the neutral beams have been upgraded to achieve higher heating power. Understanding if and how the deposition of heating power from the neutral beams has changed with these upgrades will have an impact on the coming JET campaigns and on ITER operation. In this work we report numerical simulations which study the effect of the upgraded JET NBI and tungsten impurity content on beam deposition.We compare the deposition from the old and the upgraded beam configurations in plasmas with the C-wall and the ILW. Furthermore, we investigate the effect of an asymmetrically distributed tungsten impurity on beam stopping. We use the orbit-following code ASCOT, coupled to the JETTO transport code, to calculate the beam deposition including the slowing-down and pitch and scattering of the beam ions. To take into account the effect of tungsten, ASCOT has been updated to use the ADAS database to obtain effective beam stopping coefficients. The results of ASCOT are compared with the PENCIL code, in order to determine the significance of fast ion orbit effects.

The behaviour of tungsten in the core of hybrid scenario plasmas in JET with the ITER-like wall is analyzed and modelled with a combination of neoclassical and gyrokinetic codes. In these discharges, good confinement conditions can be maintained only for the first 2 - 3 seconds of the high power phase. Later W accumulation is regularly observed, often accompanied by the onset of magnetohydrodynamical activity, in particular neoclassical tearing modes (NTMs), both of which have detrimental effects on the global energy confinement. The dynamics of the accumulation process is examined, taking into consideration the concurrent evolution of the background plasma profiles, and the possible onset of NTMs. Two time slices of a representative discharge, before and during the accumulation process, are analysed with two indipendent methods, in order to reconstruct the W density distribution over the poloidal cross-section. The same time slices are modelled, computing both neoclassical and turbulent transport components and consistently including the impact of centrifugal effects, which can be significant in these plasmas, and strongly enhanceW neoclassical transport. The modelling closely reproduces the observations and identifies inward neoclassical convection due to the density peaking of the bulk plasma in the central region as the main cause of the accumulation. The analysis of a large set of discharges provides clear indications that this effect is generic in this scenario. The unfavorable impact of the onset of NTMs on the W behaviour, observed in several discharges, is suggested to be a consequence of a detrimental combination of the effects of neoclassical transport and of the appearance of an island.

In JET C and W/Be wall experiments, the use of ELM pacing at high ELM frequency as a tool to mitigate the ELM impact on plasma facing components and for impurity control has been successfully investigated. To improve the understanding of ELM mitigation mechanisms at JET in view of ITER and to examine dependencies of the ELM trigger efficiency on available actuators, modelling schemes are required, combining the evolution of the plasma core, edge and SOL and the analysis of MHD stability in an integrated way. The JET transport suite of codes JINTRAC has been used in fully integrated modeto study and assess physical processes that appear to be relevant in case of ELMs triggered (a) by application of magnetic field perturbations that cause a sudden displacement of the plasma ("kicks") and (b) by injection of pellets. Whereas induced edge current perturbations were found to be relevant to destabilise the plasma edge in case (a), local and plasmoid-driven pressure perturbations are held responsible for the appearance of an ELM in case (b). In the context of previous integrated simulation studies of ELM pacing / mitigation by kicks and pellets at JET, recent advances are reported on the following subjects: ­ ELM mitigated regimes are analysed with JINTRAC in fully integrated mode in a refined way using a new tool for the evaluation of the MHD stability at runtime with HELENA+MISHKA. ­ The effect of kicks at low vs. high kick amplitude / gas fuelling rate in JET C and W/Be wall discharges on MHD stability is analysed and compared against experimental findings with JINTRAC+CREATE-NL.

The N2-seeding experiments at JET were carried out in order to develop a type-I ELMy H-mode reference scenario for achieving Q = 10 in ITER compatible with the wall materials (Be main chamber, W divertor) of active operation. One objective of the experiments was to reduce the steady-state divertor-target power load by introducing a radiating extrinsic impurity (N2). An unexpected feature of N2-seeding, in high-triangularity (d) JET with an ITER-Like wall (JET-ILW) plasmas, was the observation of improved pedestal confinement at levels closer to those of JET with Carbon-Fibre-Composite Wall (JET-C). It has been suggested that the level of C and its associated radiation could have been a hidden parameter in the JET-C confinement behaviour of high-d plasmas and that this could partially be recovered by N2 seeding in JET-ILW. Detailed integrated modelling (core and SOL) of these JET-ILW discharges, with and without N2 seeding, may shed some light on the difference in plasma dynamics between high- and low-d configurations and, in particular, the improvement in confinement with high-d and N2-seeding. It is important to compare the simulations with a set of experimental parameters in the core/edge/SOL to ascertain the main physics governing these plasmas has been captured correctly. This paper reports on the present results.

Since the realization that the ozone protective layer was at risk from the build‐up of anthropogenic trace gases in the atmosphere, there has been an increased interest in understanding the trends and variability of the solar UV radiation received at the surface of the earth. But during the last few decades an unfolding controversy has risen. It was found out that the exposure to the solar UVB radiation is responsible for the cutaneous production of Vitamin D, a vitamin which is essential for the bone metabolism and for the calcium and phosphorus homeostasis. For this research study, we have processed quality‐checked spectral UV irradiance measurements from three European stations (Jokioinen, Finland, Bilthoven, The Netherlands, and Thessaloniki, Greece) and the vitamin D effective doses (VDED) are calculated. As expected, the maximum VDED are observed during the second half of June, revealing the dominant effect of low solar zenith angles and cloudiness. Also the average VDED at local noon reveal that the cutaneous production of the Vitamin D can be feasible throughout the year in Bilthoven and Thessaloniki. Even for an exposure of one hour around local noon the proposed vitamin D standard dose (SDD) cannot be attained for all skin types under physiological atmospheric conditions at Jokioinen and Bilthoven.

A mobile digital rights management platform is proposed that follows the DRM reference architecture while including several important functions lacking in the OMA DRM. The platform provides strong protection methods utilizing encryption and digital watermarking, and supports content super distribution with peer-to-peer networking and Bluetooth. Licenses for defining content usage rights are acquired from license servers with a license negotiation subsystem of the client. The DRM Player software has been implemented into a smart phone and tested with many applications

Background and Objectives: An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 μg of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. Methods: One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Results: Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. Conclusion: It was concluded that the devices tested were equivalent in terms of efficacy and safety.