1. |
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2. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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4. |
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5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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6. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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7. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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8. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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9. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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11. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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12. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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13. |
- Wilkinson, Mark D., et al.
(författare)
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Comment : The FAIR Guiding Principles for scientific data management and stewardship
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders-representing academia, industry, funding agencies, and scholarly publishers-have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
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14. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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15. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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16. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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17. |
- Da Silva, Adrien, et al.
(författare)
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Laser Metal Wire drop-by-drop Deposition: a material and dilution investigation
- 2021
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Ingår i: IOP Conference Series: Materials Science and Engineering. - : Institute of Physics (IOP).
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Konferensbidrag (refereegranskat)abstract
- Additive Manufacturing has become a field of high interest in the industry, mostly due to its strong freedom of design and its flexibility. Numerous Additive Manufacturing techniques exist and present different advantages and disadvantages. The technique investigated in this research is a drop-by-drop deposition alternative to Laser Metal Wire Deposition. This technique is expected to induce a better control over the power input in the material, resulting in a better power efficiency and tailorable material properties. The aim of this research is to investigate selected material properties of the structures produced with the drop-by-drop deposition technique. Multi-drops structures were deposited from 316L, Inconel 625 (NW6625) and AlSi5 (AW4043) wires. Two drop deposition methods were investigated: (i) a contactless recoil pressure driven detachment for 316L and Inconel 625, (ii) a contact-based surface tension driven detachment for AlSi5. A material characterization including optical microscopy, EDS and hardness measurements was performed in transverse and longitudinal cross-sections. The microstructure of the deposited material, the dilution with the substrate and the heat affected zone were analysed. The contactless detachment showed a higher dilution than the contact-based technique due to the laser irradiating the substrate between two drop detachments, which melts the substrate that then mixes with the deposited drops.
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18. |
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19. |
- Griswold, Max G., et al.
(författare)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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20. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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21. |
- Kappos, Ludwig, et al.
(författare)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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22. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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23. |
- López-Fauqued, M., et al.
(författare)
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Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
- 2019
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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24. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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25. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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26. |
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27. |
- Abdo, A. A., et al.
(författare)
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Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
- 2011
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
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Tidskriftsartikel (refereegranskat)abstract
- The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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28. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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29. |
- Araujo, M. G., et al.
(författare)
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Ridge alterations following grafting of fresh extraction sockets in man. A randomized clinical trial
- 2015
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161. ; 26:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate dimensional alterations of the alveolar ridge that occurred following tooth extraction at sites grafted with Bio-Oss((R)) Collagen. Material and methodsTwenty-eight subjects with maxillary incisors, canines, and premolars scheduled for extraction were included. The tooth was carefully removed. The patients were randomly assigned to a test or a control group. In the test group patients, Bio-Oss((R)) Collagen was placed in the fresh extraction socket while in the controls no grafting was performed. Radiographic examination (cone beam computed tomograms, CBCT) was performed immediately after tooth extraction and socket treatment. Four months later, a new CBCT was obtained. In the radiographs, (i) the distance (mm) between base of the alveolar process (apex) and the buccal and palatal crests was determined, (ii) the outer profile of alveolar process of the experimental sites was outlined, and the cross section of the area (mm(2)) determined. ResultsAfter 4months of healing, the buccal and to a less extent also the palatal bone plate had become markedly reduced in height. The placement of a biomaterial in the socket failed to prevent resorption of the buccal and palatal bone walls. The cross-sectional area of the control ridge was reduced about 25% and of the test ridge with 3%. ConclusionThe placement of a xenograft in fresh extraction sockets markedly counteracted the reduction in the hard tissue component of the edentulous sites.
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30. |
- Axcrona, Karol, et al.
(författare)
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Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.
- 2012
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Ingår i: BJU international. - 1464-410X. ; 110:11, s. 1721-1728
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Tidskriftsartikel (refereegranskat)abstract
- Study Type - Therapy (RCT) Level of Evidence1b What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80mg) or goserelin (3.6mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P= 0.02). • The number of patients with an IPSS change of ≥3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P= 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.
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31. |
- Beniczky, Sandor, et al.
(författare)
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Standardized Computer-based Organized Reporting of EEG: SCORE
- 2013
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:6, s. 1112-1124
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Tidskriftsartikel (refereegranskat)abstract
- The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, episodes (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.
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32. |
- Beniczky, Sándor, et al.
(författare)
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Standardized computer-based organized reporting of EEG : SCORE - Second version
- 2017
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 128:11, s. 2334-2346
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Tidskriftsartikel (refereegranskat)abstract
- Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.
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33. |
- Borggren, Marie, et al.
(författare)
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Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark
- 2016
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 0889-2229 .- 1931-8405. ; 32:5, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine.
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34. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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35. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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36. |
- Da Silva, Adrien, et al.
(författare)
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Acceleration of metal drops in a laser beam
- 2021
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Ingår i: Applied Physics A. - : Springer. - 0947-8396 .- 1432-0630. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Different processes require the detachment of metal drops from a solid material using a laser beam as the heat source, for instance laser drop generation or cyclam. These techniques imply that the drops enter the laser beam, which might affect their trajectory. Also, many laser processes such as laser welding or additive manufacturing generate spatters that can be accelerated by the laser beam during flight and create defects on the material. This fundamental study aims at investigating the effects of a continuous power laser beam on the acceleration of intentionally detached drops and unintentionally detached spatters. Two materials were studied: 316L steel and AlSi5 aluminium alloy. High-speed imaging was used to measure the position of the drops and calculate their acceleration to compare it to theoretical models. Accelerations up to 11.2 g could be measured. The contributions of the vapor pressure, the recoil pressure, and the radiation pressure were investigated. The recoil pressure was found to be the main driving effect but other phenomena counteract this acceleration and reduce it by an order of magnitude of one to two. In addition, two different vaporization regimes were observed, resulting respectively in a vapor plume and in a vapor halo around the drop.
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37. |
- Da Silva, Adrien, et al.
(författare)
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Additive Manufacturing by laser-assisted drop deposition from a metal wire
- 2021
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 209
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Tidskriftsartikel (refereegranskat)abstract
- The subject of Additive Manufacturing includes numerous techniques, some of which have reached very high levels of development and are now used industrially. Other techniques such as Micro Droplet Deposition Manufacture are under development and present different manufacturing possibilities, but are employed only for low melting temperature metals. In this paper, the possibility of using a laser-based drop deposition technique for stainless-steel wire is investigated. This technique is expected to be a more flexible alternative to Laser Metal Wire Deposition. Laser Droplet Generation experiments were carried out in an attempt to accurately detach steel drops towards a desired position. High-speed imaging was used to observe drop generation and measure the direction of detachment of the drops. Two drop detachment techniques were investigated and the physical phenomena leading to the drop detachment are explained, wherein the drop weight, the surface tension and the recoil pressure play a major role. Optimised parameters for accurate single drop detachment were identified and then used to build multi-drop tracks. Tracks with an even geometry were produced, where the microstructure was influenced by the numerous drop depositions. The tracks showed a considerably higher hardness than the base wire, exhibiting a relatively homogeneous macro-hardness with a localised softening effect at the interfaces between drops.
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38. |
- Da Silva, Adrien
(författare)
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Aspects of material and heat transfer in drop- and powder-based laser additive manufacturing
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing became a major research topic and part of industrial production in the past years. Numerous techniques now allow to build 3D structures with a wide choice of materials. When it comes to processing of metals, a laser beam is often used as a heat source to melt either a wire or powder. Novel approaches of material deposition are also developed, such as Laser Droplet Generation, which could potentially be applied to Additive Manufacturing. During the process, the laser beam light is partly absorbed by the material, and is then converted to heat, which can induce melting and even vaporization. Additive Manufacturing presents several processing challenges, such as the recoil pressure acting on the drops and powder particles that affects their trajectory. Storage and recycling of the powders is also an important aspect since the powder properties are changed through aging. Another challenge is the adjustment of process parameters according to varying deposition conditions, where the use of process monitoring techniques is crucial.Therefore, this thesis aims at better understanding (i) the effects of recoil pressureon metal drops and powder particles, (ii) powder aging and its effects on the process, and (iii) process optimisation and stability via monitoring. In the six adjoined papers, high-speed imaging and thermal imaging were used to observe laser Additive Manufacturing processes involving both metal drops and powders. The videos enabled to observe drop detachments, measure trajectories, plot powder density maps, quantify powder catchment in the melt pool, measure themelt pool geometry, detect oxides, and extract cooling rates. The experimental results were supplemented with material analysis and theoretical calculations of thermodynamics, recoil pressure and surface tension.These studies allowed to conclude that the recoil pressure induced by laser irradiation on a drop or a powder particle can have some significant effect such as acceleration, change of trajectory, or disintegration. However, these effects seem to be considerably lower than what theoretical models predict. It was also found that the recoil pressure can be used to accurately detach drops from a wire, which was utilised as a new material deposition method for Additive Manufacturing. In Directed Energy deposition, it was showed that aging of the aluminium powder feedstock should be avoided since it induces high porosity, high dilution and decreased mechanical properties. Finally, to guarantee a defect-free deposition during the whole process, it was demonstrated that a thermal camera can be used to monitor the melt pool size, which allows to apply appropriate laser power adjustments to compensate for changing building conditions.
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39. |
- Da Silva, Adrien, et al.
(författare)
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Influence of aluminium powder aging on Directed Energy deposition
- 2022
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- The use of aluminium alloys for Additive Manufacturing is of high interest for advanced geometries and lightweight applications. In Directed Energy Deposition, a powder stock is processed with a laser beam, which offers a high process flexibility. However, aging of the powder feedstock during storage or after recycling remains fundamentally challenging for aluminium alloys because of their sensitivity to oxida-tion and porosity. In order to investigate these effects, AlSi10Mg powder batches were aged in different conditions and processed by Directed Energy Deposition. The results showed that powder aging does not significantly change the particle size or morphology, but it introduces more oxygen and hydrogen in the powder. The oxidation of the particles reduces the laser beam absorbance of the powder and increases wetting of the melt pool, which affects the track geometry. A 3.5 to 4.2 times higher porosity was observed in the material deposited from aged powder, which are most likely hydrogen pores causedby the increased hydrogen content in the aged powder. The tensile properties of the parts built with aged powder showed 19.0% lower yield strength, 14.2% lower ultimate strength and 99.2% higher elongation, which are most likely the results of the coarser microstructure and increased porosity.
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40. |
- Da Silva, Adrien
(författare)
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Laser-induced recoil pressure on metal drops and powder particles
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing became a major research topic and part of industrial production in the past years. Numerous techniques now allow to build 3D structures with a wide choice of materials. When it comes to processing of metals, a laser beam is often used as a heat source to melt either a wire or powder, where the trajectory of spatters and powder particles can be affected by the laser beam radiation. Laser beam irradiation is partly absorbed by the material, and is then converted to heat, which can cause melting and even vaporization. The vaporization of material induces a recoil pressure on the melt pool, which affects its geometry and dynamics. However, the effects of the recoil pressure on airborne objects such as drops and powder particles are still relatively unknown. Their different sizes and boundary conditions compared to a melt pool might affect their behaviour under high laser beam radiation. Therefore, this thesis aims at better understanding the effects of the recoil pressure on metal drops and powder particles, as well as their impacts on Additive Manufacturing processes, especially Directed Energy Deposition and Laser Metal Wire Deposition. In the three adjoined papers, high-speed imaging was used to observe (i) powder blown through a laser beam, (ii) drops falling in a laser beam, and (iii) drops detaching from a wire in a laser beam. The videos enabled to calculate the acceleration of powder particles and drops of different sizes, the density map of the powder stream, and the detachment direction of the drops. The experimental results were completed with theoretical calculations of thermodynamics, recoil pressure and surface tension. These studies allowed to conclude that the acceleration induced by the recoil pressure on a drop or a powder particle increases with decreased size. Moreover, the recoil pressure causes a slight deviation of the powder stream in Directed Energy Deposition that can induce a better powder focusing. The recoil pressure can also cause the disintegration of powder particles in the laser beam. Finally, it was shown that the recoil pressure can be used to detach drops on demand from a wire and accelerate them towards the substrate where they can be strategically deposited for building additive structures.
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41. |
- Da Silva, Adrien, et al.
(författare)
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Melt pool monitoring and process optimisation of directed energy deposition via coaxial thermal imaging
- 2023
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Ingår i: Journal of Manufacturing Processes. - : Elsevier. - 1526-6125. ; 107, s. 126-133
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Tidskriftsartikel (refereegranskat)abstract
- In Laser-based Directed Energy Deposition of metal powder, the use of optimised parameters allows the deposition of defect-free material, while diverging from these optimised parameters can typically result in high porosity, high dilution or different track geometry. One of the main challenges when building complex geometries is that the geometrical and thermal conditions of the deposition are constantly changing, which requires to adjust the process parameters during the production. In order to facilitate this process, sensors such as thermal cameras can be used to extract data from the process and adapt the parameters to keep the process stable despite external disturbances. In this research, different signals extracted from a coaxial thermal camera are investigated and compared for process optimisation. To investigate such possibilities, five overlapped tracks are deposited at constant laser powers in order to extract average pixel values as well as the melt pool area, length, width and orientation. The behaviour of each track deposition is modelled as a function of the laser power, and these models are used to calculate and test laser power reduction strategies based on different signals. The results show that the melt pool area is the most relevant signal to use for an efficient process control, resulting in a stable process with only ±1.6 % of signal variation from track to track.
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42. |
- Da Silva, Adrien, et al.
(författare)
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The influence of laser-induced recoil pressure on particles speed in Directed Energy Deposition
- 2022
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Ingår i: 12th CIRP Conference on Photonic Technologies [LANE 2022]. - : Elsevier. ; , s. 381-384
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Konferensbidrag (refereegranskat)abstract
- Directed Energy Deposition is a common Additive Manufacturing technique used for its high deposition rate, but the interactions between the powder stream and the laser beam are still not completely understood. It is known that the powder particles heat up in the laser beam and some theoretical models predict that they can reach vaporization temperature and are significantly accelerated by the recoil pressure. In order to learn more about these phenomena, AlSi10Mg powder streams were observed with a high-speed camera at different laser powers and a particle-tracking software was used to measure the speed of the particles. The results show no significant increase of particle speed near the powder focus where the powder is processed, nor further below the powder focus. The high initial speed of the particles results in a short travelling time through the laser beam and in a very small effect of the recoil pressure.
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43. |
- Da Silva, Adrien, et al.
(författare)
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Thermal monitoring for directed energy deposition of stainless steel, bronze, and cobalt-based alloy
- 2022
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 451
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Tidskriftsartikel (refereegranskat)abstract
- Laser cladding and Directed Energy Deposition are two related processes that allow the deposition of specific surface coatings and the production of additively manufactured parts. In both processes, the selection of optimised parameters results in the deposition of high-density material with low dilution. However, the thermal and geometrical conditions constantly change during the process and the parameters need to be continually adapted in order to avoid defects or poor properties. In this context, the development of closed-loop monitoring systems is crucial in order to widen the field of possible applications towards more complexity, with a more stable process and higher materials properties. In this research, the possibility of thermal monitoring with middle-wave and long-wave infra-red cameras is investigated for Directed Energy Deposition of 316L, Stellite 21 and CuSn10. The melt pool length and the cooling rate are extracted from thermal imaging while the laser power was varied, and these results are compared to the materials properties of the deposited tracks. The main results show that an increase of melt pool length results in a decrease of porosity and an increase of dilution, which induces a change of hardness. The melt pool length can be regulated by adjusting the laser power in order to keep both the porosity and the dilution within acceptable values.
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44. |
- Da Silva, Stéphanie, et al.
(författare)
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A novel topical PPARγ agonist induces PPARγ-activity in ulcerative colitis mucosa and prevents and reverses inflammation in induced-colitis models
- 2018
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 24:4, s. 792-805
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis.Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis.Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels.Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.
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45. |
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46. |
- De Angelis, A., et al.
(författare)
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Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
- 2018
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Ingår i: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
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Tidskriftsartikel (refereegranskat)abstract
- e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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47. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
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CHLORIDE CONTENTS AT THE CONCRETE-STEEL INTERFACE
- 2010
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Ingår i: Advances in Concrete Strutural Durability - Proceedings of the 2nd International Conference on Durability of Concrete Structures ICDCS2010, 24-26 November 2010, Hokkaido University, Sapporo, Japan, edited by Hiroshi Yokota, Takafumi Sugiyama and Tamon Ueda, Hokkaido University Press. - 9784832903609 ; , s. 275-284
-
Konferensbidrag (refereegranskat)abstract
- The composition and microstructure of the concrete-steel interface influences the criticalchloride content (Ccr) for initiation of pitting corrosion and can differ from the conditions inthe bulk concrete. This paper describes the development of a methodology for chlorideprofiling along the interface by means of LA-ICP-MS. SEM-EDS and XRD techniques wereused for semi-quantitative analysis of Ccr, microstructure characterization of the pittingpositions and distribution and composition of the corrosion products. A range of chloridelevels along the interface was measured by means of LA-ICP-MS showing good agreementwith the results from EDS analysis. A number of interface defects were found to influencepitting corrosion. Several Fe(III) oxy-hydroxides, including akaganeite, were identified. XRDanalysis suggested the existence of FeCl2. These corrosion products tended to accumulate atthe aggregate-paste interface and in air voids at the cement paste.
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48. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
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Chloride profiles along the concrete-steel interface
- 2013
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Ingår i: International Journal of Structural Engineering. - 1758-7328 .- 1758-7336. ; 4:1/2, s. 100-112
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Tidskriftsartikel (refereegranskat)abstract
- The composition and microstructure of the concrete-steelinterface influences the critical chloride content for initiation of pitting corrosion and these characteristics may differ from those of the bulk concrete. This paper describes the development of a methodology for chloride profiling along the interface by means of LA-ICP-MS. For semi-quantitative analysis, microstructure characterisation of the pitting positions and distribution and composition of the corrosion products, SEM-EDS and XRD techniques wereemployed. The results indicate that along the interface a range of chloride levels can be expected. These varied between 0.15–1.5 wt% of concrete with higher levels around the active corrosion sites. Good agreement has been foundbetween the results from LA-ICP-MS and EDS techniques. Interface defects strongly influenced the pitting corrosion. Several Fe(III) oxy-hydroxides accumulated at the aggregate-paste interface and in air voids at the cementpaste. XRD analysis suggested the presence of akaganeite and FeCl2 (rokuhnite).
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49. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
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Critical Conditions for Depassivation of Steel in Concrete: Interface Chloride Profiles
- 2011
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Ingår i: Nordic Concrete Research. ; Publication No. 43, s. 115-118
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Konferensbidrag (refereegranskat)abstract
- This paper describes an ongoing research project that aims to improve the knowledge and understanding of the critical conditions for depassivation of steel by studying the micro/meso-scale chloride profiles along the steel-concrete interface and correlating these with aspects of its microstructure and composition.
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50. |
- Dias Ferreira Da Silva, Nelson, 1978, et al.
(författare)
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Critical Conditions for Depassivation of Steel in Concrete: Interface Chloride Profiles and Steel Surface Condition
- 2012
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Ingår i: Nordic Concrete Research. - 0800-6377. ; 45, s. 111-123
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The composition and macrostructure of the concrete-steel interface and the surface finish of the steel are fundamental for the chloride induced corrosion initiation in reinforced concrete, with direct influence in the chloride threshold values (Cth). In this paper these characteristics were examined for vertically cast samples immersed in salt solution. After depassivation, the specimens were open for visual examination. Corrosion always initiated at the front side and surface defects were found to influence the corrosion onset. Chloride, calcium and iron profiles along the interface were drawn by means of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and higher chloride contents were measured around active corroding areas.
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