| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Reifarth, R., et al.
(author)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Conference paper (peer-reviewed)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 3. |
- Bauer, M., et al.
(author)
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Association between polarity of first episode and solar insolation in bipolar I disorder
- 2022
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In: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 160
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Journal article (peer-reviewed)abstract
- Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
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| 4. |
- Bauer, M., et al.
(author)
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Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder
- 2023
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In: International Journal of Bipolar Disorders. - 2194-7511. ; 11:1
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Journal article (peer-reviewed)abstract
- BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P <= 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
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| 5. |
- Bauer, M., et al.
(author)
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Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder
- 2021
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In: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
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Journal article (peer-reviewed)abstract
- Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
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| 6. |
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| 7. |
- Ahmed, M., et al.
(author)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
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In: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
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Journal article (peer-reviewed)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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| 8. |
- Bauer, M., et al.
(author)
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Solar insolation in springtime influences age of onset of bipolar I disorder
- 2017
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In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:6, s. 571-582
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Research review (peer-reviewed)abstract
- Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.
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| 9. |
- Wendisch, M., et al.
(author)
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Atmospheric and Surface Processes, and Feedback Mechanisms Determining Arctic Amplification: A Review of First Results and Prospects of the (AC)(3) Project
- 2023
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In: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 104:1
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Journal article (peer-reviewed)abstract
- Mechanisms behind the phenomenon of Arctic amplification are widely discussed. To contribute to this debate, the (AC)(3) project was established in 2016 (www.ac3-tr.de/). It comprises modeling and data analysis efforts as well as observational elements. The project has assembled a wealth of ground-based, airborne, shipborne, and satellite data of physical, chemical, and meteorological properties of the Arctic atmosphere, cryosphere, and upper ocean that are available for the Arctic climate research community. Short-term changes and indications of long-term trends in Arctic climate parameters have been detected using existing and new data. For example, a distinct atmospheric moistening, an increase of regional storm activities, an amplified winter warming in the Svalbard and North Pole regions, and a decrease of sea ice thickness in the Fram Strait and of snow depth on sea ice have been identified. A positive trend of tropospheric bromine monoxide (BrO) column densities during polar spring was verified. Local marine/biogenic sources for cloud condensation nuclei and ice nucleating particles were found. Atmospheric-ocean and radiative transfer models were advanced by applying new parameterizations of surface albedo, cloud droplet activation, convective plumes and related processes over leads, and turbulent transfer coefficients for stable surface layers. Four modes of the surface radiative energy budget were explored and reproduced by simulations. To advance the future synthesis of the results, cross-cutting activities are being developed aiming to answer key questions in four focus areas: lapse rate feedback, surface processes, Arctic mixed-phase clouds, and airmass transport and transformation.
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| 10. |
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| 11. |
- Amann, F., et al.
(author)
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A search for murarregamma at the level of 10-13
- 1991
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In: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
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Conference paper (peer-reviewed)abstract
- The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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| 12. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 13. |
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| 14. |
- Szymanski, J. J., et al.
(author)
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MEGA : A search for the decay mu –> e gamma
- 1994
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In: Intersections between particle and nuclear physics. Proceedings, 5th Conference, St. Petersburg, USA, May 31-June 6, 1994. ; , s. 789-792
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Conference paper (peer-reviewed)
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| 15. |
- Fabian, ID, et al.
(author)
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Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
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In: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
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Journal article (peer-reviewed)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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| 16. |
- Szymanski, J. J., et al.
(author)
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A study of the decay mu –> e gamma by the MEGA experiment
- 1996
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In: Proceedings, 9th Meeting, DPF'96, Minneapolis, USA, August 11-15, 1996. Vol. 1, 2.. ; , s. 1450-1452
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Conference paper (peer-reviewed)
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| 17. |
- Tedersoo, L., et al.
(author)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Journal article (peer-reviewed)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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| 18. |
- Teixeira, J., et al.
(author)
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Tropical and Subtropical Cloud Transitions in Weather and Climate Prediction Models : The GCSS/WGNE Pacific Cross-Section Intercomparison (GPCI)
- 2011
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In: Journal of Climate. - 0894-8755 .- 1520-0442. ; 24:20, s. 5223-5256
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Journal article (peer-reviewed)abstract
- A model evaluation approach is proposed in which weather and climate prediction models are analyzed along a Pacific Ocean cross section, from the stratocumulus regions off the coast of California, across the shallow convection dominated trade winds, to the deep convection regions of the ITCZ-the Global Energy and Water Cycle Experiment Cloud System Study/Working Group on Numerical Experimentation (GCSS/WGNE) Pacific Cross-Section Intercomparison (GPCI). The main goal of GPCI is to evaluate and help understand and improve the representation of tropical and subtropical cloud processes in weather and climate prediction models. In this paper, a detailed analysis of cloud regime transitions along the cross section from the subtropics to the tropics for the season June-July-August of 1998 is presented. This GPCI study confirms many of the typical weather and climate prediction model problems in the representation of clouds: underestimation of clouds in the stratocumulus regime by most models with the corresponding consequences in terms of shortwave radiation biases; overestimation of clouds by the 40-yr ECMWF Re-Analysis (ERA-40) in the deep tropics (in particular) with the corresponding impact in the outgoing longwave radiation; large spread between the different models in terms of cloud cover, liquid water path and shortwave radiation; significant differences between the models in terms of vertical cross sections of cloud properties (in particular), vertical velocity, and relative humidity. An alternative analysis of cloud cover mean statistics is proposed where sharp gradients in cloud cover along the GPCI transect are taken into account. This analysis shows that the negative cloud bias of some models and ERA-40 in the stratocumulus regions [as compared to the first International Satellite Cloud Climatology Project (ISCCP)] is associated not only with lower values of cloud cover in these regimes, but also with a stratocumulus-to-cumulus transition that occurs too early along the trade wind Lagrangian trajectory. Histograms of cloud cover along the cross section differ significantly between models. Some models exhibit a quasi-bimodal structure with cloud cover being either very large (close to 100%) or very small, while other models show a more continuous transition. The ISCCP observations suggest that reality is in-between these two extreme examples. These different patterns reflect the diverse nature of the cloud, boundary layer, and convection parameterizations in the participating weather and climate prediction models.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Fuchs, A., et al.
(author)
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Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
- 2018
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Journal article (peer-reviewed)abstract
- Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.
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| 23. |
- Gubili, C., et al.
(author)
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Isolation and Characterization of Polymorphic Microsatellite DNA Markers from an Amazonian White-sand Vegetation Specialist Bird, Xenopipo atronitens (Aves: Pipridae)
- 2016
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In: Wilson Journal of Ornithology. - : Wilson Ornithological Society. - 1559-4491 .- 1938-5447. ; 128:3, s. 668-672
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Journal article (peer-reviewed)abstract
- Thirteen novel polymorphic microsatellite loci were isolated and characterized from the Amazonian Black Manakin, Xenopipo atronitens. The loci were screened using 30 samples from Brazil. A total of 13 loci were variable with number of alleles per locus ranging from 2 to 17, whilst the observed and expected heterozygosities varied from 0.067-0.900 and 0.310-0.910, respectively. Five loci deviated significantly from the Hardy-Weinberg equilibrium, whereas one pair of loci deviated significantly from linkage disequilibrium. The set of markers will be a useful tool for future population genetic and kinship studies of X. atronitens, an Amazonian white-sand vegetation specialist.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Ritter, C. D., et al.
(author)
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Landscape configuration of an Amazonian island-like ecosystem drives population structure and genetic diversity of a habitat-specialist bird
- 2021
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In: Landscape Ecology. - : Springer Science and Business Media LLC. - 0921-2973 .- 1572-9761. ; 36, s. 2565-2582
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Journal article (peer-reviewed)abstract
- Context Amazonian white-sand ecosystems (campinas) are open vegetation patches which form a natural island-like system in a matrix of tropical rainforest. Due to a clear distinction from the surrounding matrix, the spatial characteristics of campina patches may affect the genetic diversity and composition of their specialized organisms, such as the small and endemic passerine Elaenia ruficeps. Objectives To estimate the relative contribution of the current extension, configuration and geographical context of campina patches to the patterns of genetic diversity and population structure of E. ruficeps. Methods We sampled individuals of E. ruficeps from three landscapes in central Amazonia with contrasting campina spatial distribution, from landscapes with large and connected patches to landscapes with small and isolated patches. We estimated population structure, genetic diversity, and contemporary and historical migration within and among the three landscapes and used landscape metrics as predictor variables. Furthermore, we estimated genetic isolation by distance and resistance within landscapes. Results We identified three genetically distinct populations with asymmetrical gene flow among landscapes and a decreasing migration rate with distance. Within each landscape, we found low differentiation without genetic isolation by distance nor by resistance. In contrast, we found differentiation and spatial correlation between landscapes. Conclusions Together with previous studies, the population dynamics of E. ruficeps suggests that both regional context and landscape structure shape the connectivity among populations of campina specialist birds. Also, the spatial distribution of Amazonian landscapes, together with their associated biota, has changed in response to climatic changes in the Late Pleistocene.
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| 28. |
- Scott, J., et al.
(author)
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Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
- 2019
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In: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 7:1
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Journal article (peer-reviewed)abstract
- Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.
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| 29. |
- de Wert, Guido, et al.
(author)
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Human germline gene editing : Recommendations of ESHG and ESHRE
- 2018
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In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 26:4, s. 445-449
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Journal article (peer-reviewed)abstract
- Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if GLGE would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique can help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. After consulting its membership and experts, this final version of the Recommendations was endorsed by the Executive Committee and the Board of the respective Societies in May 2017. Taking account of ethical arguments, we argue that both basic and pre-clinical research regarding GLGE can be justified, with conditions. Furthermore, while clinical GLGE would be totally premature, it might become a responsible intervention in the future, but only after adequate pre-clinical research. Safety of the child and future generations is a major concern. Future discussions must also address priorities among reproductive and potential non-reproductive alternatives, such as PGD and somatic editing, if that would be safe and successful. The prohibition of human germline modification, however, needs renewed discussion among relevant stakeholders, including the general public and legislators.
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| 30. |
- De Wert, G., et al.
(author)
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Responsible innovation in human germline gene editing : Background document to the recommendations of ESHG and ESHRE
- 2018
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In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 26:4, s. 450-470
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Journal article (peer-reviewed)abstract
- Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, preclinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g., gene editing goes against nature) do not seem convincing while consequentialist objections (e.g., safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.
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| 31. |
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| 32. |
- Gudowski, Waclaw, et al.
(author)
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Review of the European project - Impact of Accelerator-Based Technologies on Nuclear Fission Safety (IABAT)
- 2001
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In: Progress in nuclear energy (New series). - 0149-1970 .- 1878-4224. ; 38:1-2, s. 135-151
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Journal article (peer-reviewed)abstract
- The IABAT project - Impact of Accelerator Based Technologies on Nuclear Fission Safety - started in 1996 in the frame of 4(th) Framework Programme of the European Union, R&D specific programme Nuclear fission safety 1994-1998, area A.2 Exploring innovative approaches/Fuel cycle concepts, as one of the first common European activities in ADS. The project was completed October 31, 1999. The overall objective of the IABAT project has been a preliminary assessment of the potential of Accelerator-Driven Systems (ADS) for transmutation of nuclear waste and for nuclear energy production with minimum waste generation. Moreover, more specific topics related to nuclear data and code development for ADS have been studied in more detail. Four ADSs have been studied for different fuel/coolant combinations: liquid metal coolant and solid fuel, liquid metal coolant and dispersed fuel, and fast and thermal molten salt systems. Target studies comprised multiple target solutions and radiation damage problems in a target environment. In a tool development part of the project a methodology of subcriticality monitoring has been developed based on Feynman-alpha and Rossi-alpha methods. Moreover, a new Monte-Carlo burnup code taking full advantage of continuous neutron cross-section data has been developed and benchmarked. Impact on the risk from high-level waste repositories fi om radiotoxicity reduction using ADS has been assessed giving no crystal-clear benefits of ADS for repository radiotoxicity reduction but concluding some important prerequisites for effective transmutation. In proliferation studies important differences between critical reactors and ADS have been underlined and non-proliferation measures have been proposed. In assessment of accelerator technology costing models have been created that allow the circular and linear accelerator options to be compared and the effect of parameter variations examined. The calculations reported show that cyclotron systems would be more economical, due mainly to the advantage of the cost of RF power supplies. However, the accelerator community regards with skepticism the possibility of transporting and extracting more than a 10mA beam current from a 1GeV cyclotron and therefore technical factors may limit the application of cyclotrons. Finally, this review summarizes development of nuclear data in the energy region between 20 Mev and 150 MeV. Neutron and proton transport data files for Fe, Ni, Pb, Th, U-238 and Pu-239 have been created. The high-energy part of the data files consists completely of results from model calculations, which are benchmarked against the available experimental data. Although there is obviously future work left regarding fine-tuning of several parts of the data files, the representation of nuclear reaction information up to 150 MeV is already better than can be attained with intranuclear cascade codes.
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| 33. |
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| 34. |
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| 35. |
- Pearce, Neil E, et al.
(author)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 36. |
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| 37. |
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| 38. |
- Amare, Azmeraw T, et al.
(author)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 39. |
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| 40. |
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| 41. |
- Ben, Rayana M.C., et al.
(author)
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Guidelines for sampling, measuring and reporting ionized magnesium in undiluted serum, plasma or blood : International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
- 2005
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In: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 43:5, s. 564-569
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Journal article (peer-reviewed)abstract
- All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium. © 2005 by Walter de Gruyter.
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| 42. |
- Bredin, Y. K., et al.
(author)
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Above- and below-ground biodiversity responses to the prolonged flood pulse in central-western Amazonia, Brazil
- 2022
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In: Environmental DNA. - : Wiley. - 2637-4943. ; 4:3, s. 533-548
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Journal article (peer-reviewed)abstract
- Amazonia encompasses extensive forests in areas that are periodically inundated by overflowing rivers. The inundation depth and duration vary according to the slope of the terrain and distance to major water bodies. This creates a flooding gradient from the lowest lying seasonally flooded forest up into the unflooded forest, which directly affects the biota. However, the effect of this gradient on soil organisms remains elusive. Here, we use DNA metabarcoding to estimate prokaryote and eukaryote diversity from soil and litter samples along the flooding gradient in central-western Amazonia using 16S and 18S gene sequences, respectively. We characterize the below-ground diversity and community composition based on amplicon sequence variants (ASVs). We examine relationships between the soil biota and the flooding gradient, soil properties, and above-ground woody plant diversity. The flooding gradient does not explain below-ground biodiversity, nor is below-ground diversity explained by the above-ground woody plant diversity. We uncover several taxonomic groups—such as Patescibacteria—not previously reported from Amazonian seasonally flooded forests. The flooding gradient and woody plant diversity partly explain the community composition of soil bacteria. Although the effects of the flooding gradient, soil properties, and above-ground woody plant diversity are difficult to quantify, our results indicate that flood stress may influence below-ground bacterial community composition. © 2021 The Authors. Environmental DNA published by John Wiley & Sons Ltd.
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| 43. |
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| 44. |
- de Wert, Guido, et al.
(author)
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Human germline gene editing. Recommendations of ESHG and ESHRE
- 2018
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In: HUMAN REPRODUCTION OPEN. - : Oxford University Press (OUP). - 2399-3529. ; 2018:1
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Journal article (peer-reviewed)abstract
- Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if GLGE would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique can help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. After consulting its membership and experts, this final version of the Recommendations was endorsed by the Executive Committee and the Board of the respective Societies in May 2017. Taking account of ethical arguments, we argue that both basic and pre-clinical research regarding human GLGE can be justified, with conditions. Furthermore, while clinical GLGE would be totally premature, it might become a responsible intervention in the future, but only after adequate pre-clinical research. Safety of the child and future generations is a major concern. Future discussions must also address priorities among reproductive and potential non-reproductive alternatives, such as PGD and somatic editing, if that would be safe and successful. The prohibition of human germline modification, however, needs renewed discussion among relevant stakeholders, including the general public and legislators.
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| 45. |
- de Wert, Guido, et al.
(author)
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Responsible innovation in human germline gene editing. Background document to the recommendations of ESHG and ESHRE
- 2018
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In: HUMAN REPRODUCTION OPEN. - : Oxford University Press (OUP). - 2399-3529. ; 2018:1
-
Journal article (peer-reviewed)abstract
- Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, pre-clinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g. gene editing goes against nature) do not seem convincing while consequentialist objections (e.g. safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.
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| 46. |
- Frederiksen, K. S., et al.
(author)
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A European Academy of Neurology guideline on medical management issues in dementia
- 2020
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:10, s. 1805-1820
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Journal article (peer-reviewed)abstract
- Background and purpose: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. Methods: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. Results: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk–benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement). Conclusion: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.
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| 47. |
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| 48. |
- Koike, M., et al.
(author)
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Year-Round In Situ Measurements of Arctic Low-Level Clouds : Microphysical Properties and Their Relationships With Aerosols
- 2019
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 124:3, s. 1798-1822
-
Journal article (peer-reviewed)abstract
- Two years of continuous in situ measurements of Arctic low-level clouds have been made at the Mount Zeppelin Observatory (78 degrees 56N, 11 degrees 53E), in Ny-angstrom lesund, Spitsbergen. The monthly median value of the cloud particle number concentration (N-c) showed a clear seasonal variation: Its maximum appeared in May-July (658cm(-3)), and it remained low between October and March (87cm(-3)). At temperatures warmer than 0 degrees C, a clear correlation was found between the hourly N-c values and the number concentrations of aerosols with dry diameters larger than 70nm (N-70), which are proxies for cloud condensation nuclei (CCN). When clouds were detected at temperatures colder than 0 degrees C, some of the data followed the summertime N-c to N-70 relationship, while other data showed systematically lower N-c values. The lidar-derived depolarization ratios suggested that the former (CCN-controlled) and latter (CCN-uncontrolled) data generally corresponded to clouds consisting of supercooled water droplets and those containing ice particles, respectively. The CCN-controlled data persistently appeared throughout the year at Zeppelin. The aerosol-cloud interaction index (ACI=dlnN(c)/(3dlnN(70))) for the CCN-controlled data showed high sensitivities to aerosols both in the summer (clean air) and winter-spring (Arctic haze) seasons (0.220.03 and 0.250.02, respectively). The air parcel model calculations generally reproduced these values. The threshold diameters of aerosol activation (D-act), which account for the N-c of the CCN-controlled data, were as low as 30-50nm when N-70 was less than 30cm(-3), suggesting that new particle formation can affect Arctic cloud microphysics.
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| 49. |
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| 50. |
- Ritter, C., et al.
(author)
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Microphysical properties and radiative impact of an intense biomass burning aerosol event measured over Ny-angstrom lesund, Spitsbergen in July 2015
- 2018
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In: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 70
-
Journal article (peer-reviewed)abstract
- In this work, an evaluation of an intense biomass burning event observed over Ny-angstrom lesund (Spitsbergen, European Arctic) in July 2015 is presented. Data from the multi-wavelengths Raman-lidar KARL, a sun photometer and radiosonde measurements are used to derive some microphysical properties of the biomass burning aerosol as size distribution, refractive index and single scattering albedo at different relative humidities. Predominantly particles in the accumulation mode have been found with a bi-modal distribution and dominance of the smaller mode. Above 80% relative humidity, hygroscopic growth in terms of an increase of particle diameter and a slight decrease of the index of refraction (real and imaginary part) has been found. Values of the single scattering albedo around 0.9 both at 355nm and 532nm indicate some absorption by the aerosol. Values of the lidar ratio are around 26sr for 355nm and around 50sr for 532nm, almost independent of the relative humidity. Further, data from the photometer and surface radiation values from the local baseline surface radiation network (BSRN) have been applied to derive the radiative impact of the biomass burning event purely from observational data by comparison with a clear background day. We found a strong cooling for the visible radiation and a slight warming in the infra-red. The net aerosol forcing, derived by comparison with a clear background day purely from observational data, obtained a value of -95 W/m(2) per unit AOD500.
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