| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
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| 3. |
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| 4. |
- Alström, Per, Professor, et al.
(författare)
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Morphology, vocalizations, and mitochondrial DNA suggest that the Graceful Prinia is two species
- 2021
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Ingår i: Ornithology. - : Oxford University Press (OUP). - 0004-8038 .- 2732-4613 .- 1938-4254. ; 138:2
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Tidskriftsartikel (refereegranskat)abstract
- Prinias (Cisticolidae:Prinia) are resident warblers of open areas across Africa and Asia and include many polytypic species whose species limits have not been seriously reevaluated recently. Based on an integrative taxonomic analysis of morphology, song, and mitochondrial DNA (mtDNA), we suggest that 2 species should be recognized in the Graceful Prinia (Prinia gracilis) complex. In addition, our morphological analyses show the existence of a well-marked undescribed form in southeastern Somalia, which we name herein as a new subspecies. Prinia gracilisis a small, drab, long-tailed species with streaking above and plain pale underparts that has been suggested to fall into 2 groups: the southwestern nominate group (from Egypt to Oman) and the northeastern lepida group (from Turkey through India). However, the characters presented to justify this grouping are variable and show a mosaic pattern, and whether genetic and vocal differences exist is unknown. We found consistent between-group song differences, with the nominate group giving consistently longer inter-phrase intervals, whereas the members of the lepida group sing an essentially continuous reel. An mtDNA tree suggests a deep split between the nominate and lepida groups, with a coalescence time between these clades of similar to 2.2 million years ago. Vocal and mtDNA analyses provided evidence that the northeastern Arabian Peninsula taxon carpenteri belongs to the lepida group. We found that, of all the morphological characters proposed, only proportions and tail barring and spotting relatively consistently distinguish the 2 groups. However, these characters strongly suggest that the eastern Arabian Peninsula is populated by taxa of both the gracilis and lepida groups, in different areas, but we lack genetic and bioacoustic data to corroborate this. Although further study is needed in potential contact zones, we suggest that 2 species should be recognized in the P. gracilis complex, and we propose the retention of the English name Graceful Prinia for P. gracilis sensu stricto, while we suggest that P. lepida be known as Delicate Prinia.
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| 5. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 6. |
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| 7. |
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| 8. |
- Andreasson, Jesper, 1977-, et al.
(författare)
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Våldsbejakande extremism och radikalisering: En översikt : [Violent extremism and radicalization: an overview]
- 2018
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Ingår i: Young, Marginalised but not Radicalised. - London : IARS Publications. - 9781907641466 ; , s. 152-175
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden, the understanding of processes of radicalization and the development of preventive work against violent extremism can be said to be framed by a few specific political decisions that were formative for the policies developed. These are dealt with in the text. Among other things, the result shows that the security discourse and preventive work are often mixed up at the policy level, which has repercussions in research and prevention. One important key to developing the work on security and prevention lies in the need for further knowledge development regarding everything from methods and field studies to policy practices. Apart from providing an account of developments in Sweden, there are also arguments for a more skeptical, reflexive, and critical attitude towards all forms of simplified categorizations of young people, which risks stigmatizing individuals and groups. By starting from a critical and reflexive social education perspective, it will become possible to contribute to understanding and to an analysis of social contexts, risks, and negative spirals. The ambition of trying to predict which individuals will potentially commit crimes of terror represents a dead end. On the other hand, there are possibilities of identifying risk environments, subcultural groups that cultivate extreme opinions, and then to approach these groups in various ways in order to develop effective social pedagogical work and positive and GLM-based trajectories for young people at risk for radicalisation.
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| 9. |
- Augustin, Tim, et al.
(författare)
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System Design of Fast Actuator for Vacuum Interrupter in DC Applications
- 2018
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Ingår i: 2018 28th International Symposium on Discharges and Electrical Insulation in Vacuum (ISDEIV). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538643730 ; , s. 527-530
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Konferensbidrag (refereegranskat)abstract
- One of the major challenges of DC circuit breakers is the required fast mechanical actuator. In this paper, a Thomson coil actuator system for a vacuum interrupter is designed. Active damping is used to decelerate the moving contacts. Challenges are discussed, especially concerning the power supply needed for the Thomson coil actuator. The design philosophy is explained and FEM simulation results are presented. The results indicate that a wide range of combinations of drive circuit capacitance and voltage fulfill the requirements for armature acceleration. However, active damping requires a very careful selection of drive circuit voltage and timing of applied damping.
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| 10. |
- Augustin, Tim, et al.
(författare)
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Thomson-Coil Actuator System for Enhanced Active Resonant DC Circuit Breakers
- 2022
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Ingår i: IEEE Journal of Emerging and Selected Topics in Power Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-6777 .- 2168-6785. ; 10:1, s. 800-810
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced active resonant (EAR) dc circuit breakers (DCCBs) are a promising set of recently proposed DCCB concepts. As other DCCBs, EAR DCCBs still require a fast mechanical switch. The requirements on the actuator of the mechanical switch depend on the DCCB concept and the dc grid and are derived here for an EAR DCCB. Thomson-coil actuators (TCAs) can open and close mechanical switches sufficiently fast to satisfy the requirements. This work studies experimentally a TCA system with active damping for an off-the-shelf industrial vacuum interrupter used as mechanical switch in an EAR DCCB. The prototype is explained in detail, and extensive measurement results are presented, showing that active damping must be perfectly timed to be effective. A novel Thomson-coil (TC) driver is proposed and studied experimentally, which operates the TCA more efficiently by recycling energy during the actuation. Moreover, the novel TC driver reduces the capacitive storage by 50% and allows for faster recharging with lower charging current. Finally, the autoreclosing and proactive commutation operation of the TCA system and the interruption capability of the prototype EAR DCCB are demonstrated experimentally.
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| 11. |
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| 12. |
- Bissal, Ara, 1986-, et al.
(författare)
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Comparison of two Ultra-fast actuator concepts
- 2012
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Ingår i: IEEE transactions on magnetics. - : IEEE Press. - 0018-9464 .- 1941-0069. ; 48:11, s. 3315-3318
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, two different types of ultra-fast electromechanical actuators are compared using a multi-physical finite element simulation model that has been experimentally validated. They are equipped with a single-sided Thomson coil (TC) and a double-sided drive coil (DSC), respectively. The former consists of a spirally-wound flat coil with a copper armature on top, while the latter consists of two mirrored spiral coils that are connected in series. Initially, the geometry and construction of each of the actuating schemes are discussed. Subsequently, the theory behind the two force generation principles are described. Furthermore, the current, magnetic flux densities, accelerations, and induced stresses are analyzed. Moreover, mechanical loadability simulations are performed to study the impact on the requirements of the charging unit, the sensitivity of the parameters, and evaluate the degree of influence on the performance of both drives. Finally, it is confirmed that although the DSC is mechanically more complex, it has a greater efficiency than that of the TC.
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| 13. |
- Bissal, Ara, 1986-, et al.
(författare)
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Electric to Mechanical Energy Conversion of Linear Ultra-Fast Electro-Mechanical Actuators Based on Stroke Requirements
- 2014
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Ingår i: Electrical Machines (ICEM), 2014 International Conference on. - : IEEE conference proceedings. ; , s. -515
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Konferensbidrag (refereegranskat)abstract
- The operational efficiency of ultra fast actuators usedas drives in high voltage direct current breakers are at best5 %. To boost their efficiency, the design of the energizing circuitis crucial. A multi-physics finite element method (FEM) modelcoupled with a SPICE circuit model that is able to predict theperformance of the actuator with an accuracy of at least 95 % hasbeen developed and verified experimentally. Several variants ofprototypes and models have been simulated, built, and tested.It was shown that one of the main problems leading to lowefficiencies is the stroke of the drive. However, there is a possibilityto increase the efficiency of the electric to mechanical energyconversion process of the studied Thomson (TC) and double sidedcoils (DSC) to a maximum of 54 % and 88 % respectively iftheir stroke is minimized. This can be done at the expense ofincreasing the complexity and the cost of the contact system bydesigning a switch with several series connected contacts that isencapsulated in a medium with a high dielectric strength. Anotherproposed solution is to design a current pulse with a rise timethat is considerably shorter than the mechanical response time ofthe system. Parametric variations of capacitances and chargingvoltages show that the TC and the DSC can achieve efficienciesup to 15 % and 23 % respectively. Regardless of the chosenmethod, the DSC has a superior efficiency compared to a TC.
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| 14. |
- Bissal, Ara, et al.
(författare)
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Electric to Mechanical Energy Conversion of Linear Ultrafast Electromechanical Actuators Based on Stroke Requirements
- 2015
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Ingår i: IEEE transactions on industry applications. - 0093-9994 .- 1939-9367. ; 51:4, s. 3059-3067
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Tidskriftsartikel (refereegranskat)abstract
- The operational efficiency of ultrafast actuators used as drives in high-voltage direct-current breakers is at best 5%. To boost their efficiency, the design of the energizing circuit is crucial. A multiphysics finite-element method model coupled with a SPICE circuit model that is able to predict the performance of the actuator with an accuracy of at least 95% has been developed and verified experimentally. Several variants of prototypes and models have been simulated, built, and tested. It was shown that one of the main problems leading to low efficiencies is the stroke of the drive. However, there is a possibility to increase the efficiency of the electric to mechanical energy conversion process of the studied Thomson coil (TC) and double-sided coil (DSC) to a maximum of 54% and 88%, respectively, if their stroke is minimized. These efficiencies are idealistic, and these were obtained with clamped armature studies. The efficiency of the actuator can be increased at the expense of increasing the complexity and the cost of the contact system by designing a switch with several series-connected contacts that is encapsulated in a medium with a high dielectric strength. Another proposed solution is to design a current pulse with a rise time that is considerably shorter than the mechanical response time of the system. Parametric variations of capacitances and charging voltages show that the TC and the DSC can achieve efficiencies up to 15% and 23%, respectively. Regardless of the chosen method, the DSC has a superior efficiency compared to a TC.
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| 15. |
- Bissal, A., et al.
(författare)
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Hybrid multi-physics modeling of an ultra-fast electro-mechanical actuator
- 2015
-
Ingår i: Actuators. - : MDPI AG. - 2076-0825. ; 4:4, s. 314-335
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Tidskriftsartikel (refereegranskat)abstract
- The challenges of an HVDC breaker are to generate impulsive forces in the order of hundreds of kilonewtons within fractions of a millisecond, to withstand the arising internal mechanical stresses and to transmit these forces via an electrically-insulating device to the contact system with minimum time delay. In this work, several models were developed with different levels of complexity, computation time and accuracy. Experiments were done with two mushroom-shaped armatures to validate the developed simulation models. It was concluded that although the electromagnetic force generation mechanism is highly sensitive to the mechanical response of the system, the developed first order hybrid model is able to predict the performance of the breaker with good accuracy.
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| 16. |
- Bissal, Ara, 1986-, et al.
(författare)
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Loadability and scaling aspects of Thomson based ultra-fast actuators
- 2012
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Ingår i: Actuator 2012.
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Konferensbidrag (refereegranskat)abstract
- In this paper, an ultra-fast single-sided Thomson based actuator is studied. The actuator is comprised of a flat spiral-shaped coil with a conductive armature in its proximity. This armature is mechanically loaded with a uniform mass distribution over its cross section. The energizing source consists of a capacitor bank that is discharged through the actuator coil resulting in a high magnetic pressure within fractions of a millisecond. The coil is dimensioned to withstand the temperature rise.An experimentally validated multi-physical finite element model is used to perform simulations by varying the mechanical load to explore the performance of the actuator topology. The obtained currents, induced forces, stresses, and accelerations of the armature are then analyzed in an attempt to develop scaling techniques that can predict for example velocity and efficiency. Finally, the results of the scaling techniques are presented and compared to each other.
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| 17. |
- Bissal, Ara, et al.
(författare)
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Multiphysics modeling and experimental verification of ultra-fast electro-mechanical actuators
- 2015
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Ingår i: International journal of applied electromagnetics and mechanics. - 1383-5416 .- 1875-8800. ; 49:1, s. 51-59
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a multi-physics computational tool has been developed to accurately model and build high performance ultra-fast actuators. The research methodology is based on a finite element method model coupled with a circuit model. Electromagnetic, thermal, mechanical, and algebraic equations are implemented in Comsol Multiphysics and verified with laboratory experiments of a built prototype. A simplified model is preferred as long as its underlying assumptions hold. However, in the presence of large current and force densities, nonlinearities such as deformations may occur. Such phenomena can only be captured by the use of the developed comprehensive multi-physics simulation model. Although this model is computationally demanding, it was shown to have an accuracy of at least 95% when compared with experiments.
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| 18. |
- Bissal, Ara, et al.
(författare)
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On the design of a linear composite magnetic damper
- 2015
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Ingår i: 2015 IEEE International Magnetics Conference, INTERMAG 2015. - : IEEE conference proceedings. - 9781479973224
-
Konferensbidrag (refereegranskat)abstract
- In recent years, ultra-fast actuators have become key elements in the development of high voltage direct current (HVDC) breakers for multiterminal grids which represent a huge progress in modern power transmission [1]. After fulfilling their operation these actuators need to be decelerated using controllable forces to avoid deforming vital components incorporated in the system. In this paper, a dedicated damper is proposed based on a magnet array that induces eddy currents in a composite metal tube resulting in an efficient braking response. Several topologies are investigated by simulations and experiments. The theory behind eddy current damping is explained in [2]. The main requirements for such dampers are reliability, robustness, and ease of construction. The expected durability of these kind of dampers is longer than the breaker itself which guarantees extremely good reliability within HVDC systems.
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| 19. |
- Bissal, Ara, et al.
(författare)
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On the Design of a Linear Composite Magnetic Damper
- 2015
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Ingår i: IEEE transactions on magnetics. - : IEEE Press. - 0018-9464 .- 1941-0069. ; 51:11
-
Tidskriftsartikel (refereegranskat)abstract
- High-voltage direct current (HVdc) breakers are the key components in the realization of multiterminal HVdc grids. In the presence of fault current, these breakers should be able to deliver impulsive forces to swiftly open the metallic contacts. After the acceleration phase, the moving armature should be decelerated using controllable forces to avoid plastically deforming fragile components integrated in the system. In this paper, finite-element method-based simulation models, complimented with small-scale and large-scale experimental prototypes, were utilized to benchmark different damping topologies. It was found that a Halbach-based configuration can deliver a damping force that is almost two and a half times larger than its sequel. Its sequel, composed of vertically stacked oppositely oriented magnets, is easier to assemble and is also capable of generating a considerable damping force. Finally, it has been shown that both these schemes, inserted in a composite tube, have a potential to be used as dampers in HVdc breakers.
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| 20. |
- Bissal, Ara, 1986-, et al.
(författare)
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On the Design of Ultra-Fast Electromechanical Actuators : A Comprehensive Multi-Physical Simulation Model
- 2012
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Ingår i: Sixth International Conference on Electromagnetic Field Problems and Applications (ICEF), 2012. - : IEEE conference proceedings. - 9781467313339 ; , s. 1-4
-
Konferensbidrag (refereegranskat)abstract
- In this paper, a simulation of an ultra-fast electromechanical drive was performed by using a two-dimensional axi-symmetric multi-physical finite element model. The aim of this paper is to primarily show that the following model can be used to simulate and design those actuators with good accuracy, secondly, to study the behavior and sensitivity of the system and thirdly, to demonstrate the potential of the model for industrial applications. The simulation model is coupled to a circuit and solves for the electro-magnetic, thermal, and mechanical dynamics utilizing a moving mesh. The actuator under study is composed of a spiral-shaped coil and a disk-shaped 3mm thick copper armature on top. Two numerical studies of such an actuator powered by 2640 J capacitor banks were performed. It is shown that forces up to 38 kN can be achieved in the range of 200 μs. To add credibility, a benchmark prototype was built to validate this experimentally with the use of a high speed camera and image motion analysis.
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| 21. |
- Bissal, Ara, et al.
(författare)
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Optimal Energizing Source Design for Ultra-Fast Actuators
- 2013
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Konferensbidrag (refereegranskat)abstract
- One of the key enabling technologies for multi-terminal HVDCgrids is the existence of a breaker that can operate withina few milliseconds. A lot of research has been done to builddifferent ultra-fast drives to actuate the electric contacts ofthese breakers. What they all have in common is an operationalefficiency of at best 5 %. Capacitor banks are discharged throughspirally shaped flat coils to generate ultra-fast repulsive forces. Tooptimize the efficiency of the drive, the design of the energizingcircuit is crucial. The aim of this paper is to optimize theenergizing source and provide a deep explanation of the effectof the chosen capacitance and charging voltage for two actuatorconcepts, the Thomson coil (TC) and the double sided coil (DSC)for different stroke requirements. An experimentally validatedmulti-physics finite element method (FEM) simulation model is applied.
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| 22. |
- Borgström, Magnus, et al.
(författare)
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Nanowires With Promise for Photovoltaics
- 2011
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - 1077-260X. ; 17:4, s. 1050-1061
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Tidskriftsartikel (refereegranskat)abstract
- Solar energy harvesting for electricity production is regarded as a fully credible future energy source: plentiful and without serious environmental concerns. The breakthrough for solar energy technology implementation has, however, been hampered by two issues: the conversion efficiency of light into electricity and the solar panel production cost. The use of III-V nanowires (NWs) in photovoltaics allows to respond to both these demands. They offer efficient light absorption and significant cost reduction. These low-dimensional structures can be grown epitaxially in dense NW arrays directly on silicon wafers, which are abundant and cheaper than the germanium substrates used for triple-junction solar cells today. For planar structures, lattice matching poses a strong restriction on growth. III-V NWs offer to create highly efficient multijunction devices, since multiple materials can be combined to match the solar spectrum without the need of tightly controlled lattice matching. At the same time, less material is required for NW-based solar cells than for planar-based architecture. This approach has potential to reach more than 50% in efficiency. Here, we describe our work on NW tandem solar cells, aiming toward two junctions absorbing different parts of the solar spectrum, connected in series via a tunnel diode.
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| 23. |
- Corea-Araujo, Javier A., et al.
(författare)
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Optimum design of hybrid HVDC circuit breakers using a parallel genetic algorithm and a MATLAB-EMTP environment
- 2017
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Ingår i: IET Generation, Transmission & Distribution. - : INST ENGINEERING TECHNOLOGY-IET. - 1751-8687 .- 1751-8695. ; 11:12, s. 2974-2982
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Tidskriftsartikel (refereegranskat)abstract
- The optimum design of power system components is becoming a relevant topic in power system studies. Genetic algorithms (GAs) are considered as a proper approach for optimisation problems in which non-linear elements are involved. Several trends are presently leading GAs to a new level; for instance, its combination with parallel computing can facilitate the solution of problems where individual evaluations of the fitness function require an important computational effort. This study presents a procedure based on a MATLAB-EMTP application and the usage of a multicore environment for the optimum selection of hybrid high-voltage DC (HVDC) circuit breaker parameters; the goal is to obtain a transient response of the hybrid design with voltages, currents and fault clearance times within specified limits.
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| 24. |
- Crespo, M. M., et al.
(författare)
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ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part III: Pharmacology, medical and surgical management of post-transplant extrapulmonary conditions statements
- 2021
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 40:11, s. 1279-1300
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Tidskriftsartikel (refereegranskat)abstract
- Patients with connective tissues disease (CTD) are often on immunomodulatory agents before lung transplantation (LTx). Till now, there's no consensus on the safety of using these agents perioperative and post-transplant. The International Society for Heart and Lung Transplantation-supported consensus document on LTx in patients with CTD addresses the risk and contraindications of perioperative and post-transplant management of the biologic disease-modifying antirheumatic drugs (bDMARD), kinase inhibitor DMARD, and biologic agents used for LTx candidates with underlying CTD, and the recommendations and management of non-gastrointestinal extrapulmonary manifestations, and esophageal disorders by medical and surgical approaches for CTD transplant recipients. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.
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| 25. |
- Dellgren, Goeran, et al.
(författare)
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Effect of once-per-daytacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial
- 2024
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Ingår i: LANCET RESPIRATORY MEDICINE. - 2213-2600. ; 12:1, s. 34-44
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (005-01 mg/kg before transplantation and 01-02 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). Findings Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 552 years (SD 102), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 028 [95% CI 015-052], log-rank p<00001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 072 [95% CI 041-127], log-rank p=025). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 049 [95% CI 026-091], log-rank p=0021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. Interpretation Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.
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| 26. |
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| 27. |
- Doddapaneni, Venkatesh, et al.
(författare)
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Spectroscopic investigations of the ablated species from the polymers exposed to electric arcs in air
- 2015
-
Ingår i: 2015 3rd International Conference on Electric Power Equipment - Switching Technology, ICEPE-ST 2015. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467374149 ; , s. 337-340
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Konferensbidrag (refereegranskat)abstract
- Polymeric walls have been widely used in the last decades to improve the arc interruption process in electrical switching applications. This improvement is achieved by the evaporation (ablation) of the polymeric walls due to the highly energetic radiation generated by the electrical arcs. This experimental study deals with polymeric walls that are exposed to the electrical arcs generated between a 5 mm air gap with prospective current of 1.4 kA. In this paper, two different techniques are discussed aiming at the identification of the dominant ablated species produced during the arc interruption process, namely Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis coupled with Fourier transform infrared analysis of evolved gases (EGA). In addition, the morphological and chemical changes on the surface of the exposed polymeric walls are analyzed by microscopical techniques.
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| 28. |
- Edvardsson Rasmussen, Jesper, 1984-
(författare)
-
Inner ear proteomics and barriers : Clinical and experimental findings
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hearing is important in many aspects of life, including communication, assessing one’s surroundings, entertainment and social interaction. Hearing loss is common and according to the Global Burden of Disease Study, 5% of the global population require hearing rehabilitation (1). Pharmacological treatment options are limited, so understanding cellular mechanisms in the damaged inner ear is crucial for developing novel therapies.In this thesis, the human inner ear proteome in patients with sporadic vestibular schwannoma (VS) and its association with hearing loss were investigated. Ototoxic effects induced by furosemide were also examined, focusing on inner ear barrier function, furosemide sensitive Na-K-Cl co-transporter 1 (NKCC1), Fetuin-A, linked to tumour-associated hearing loss, and Pigment epithelium-derived factor (PEDF), potentially important for blood-endolymph barrier integrity.Translabyrinthine surgery on 35 patients, 32 with VS and three with meningioma, provided samples from perilymph, endolymph, endolymphatic sac tissue, VS biopsies and cerebrospinal fluid (CSF) for proteome analysis. Effects of furosemide on the inner ear barriers were studied in mice using 9.4Tesla MRI, and in guinea pigs using immunohistochemistry and mRNA in situ hybridisation focusing on NKCC1, Fetuin-A, and PEDF.Proteomic analysis revealed consistent sets of proteins in perilymph (91/315) and endolymph (545/1211). The proteomes of perilymph and CSF exhibited specific differences, with proteins unique to each fluid, thereby emphasizing the distinct origin of perilymph separate from CSF. Fetuin-A was inversely related to tumour-associated hearing loss, while patients with severe to profound hearing loss exhibited upregulation of complement factor H-related protein 2 (CFHR2).Furosemide compromised the blood-endolymph barrier, allowing gadolinium contrast into scala media. It affected NKCC1 of type II fibrocytes coinciding with the onset of hearing loss following high-dose furosemide, suggesting early disruption in potassium ion recirculation. Fetuin-A and PEDF were identified in the cochlea at protein and mRNA level. Their staining intensity increased in various cochlear subsites 120 minutes after furosemide administration, indicating their involvement in the cochlear response to the effects of furosemide.In summary, this thesis uncovered significant inter-individual variability in both the perilymph and endolymph proteome, alongside a consistent subset of proteins. Further, associations between hearing loss and proteome changes suggest inflammation as a potential mechanism for hearing degradation caused by vestibular schwannomas. Experimentally, impact of furosemide on blood-inner ear barriers were visualised in vivo and type II fibrocytes were identified as potential initial targets for NKCC1 blockade. Fetuin-A and PEDF were confirmed in several cell types in the cochlea and may increase in response to very high furosemide doses.
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| 29. |
- Felldin, Marie, et al.
(författare)
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Initial Report From a Swedish High-volume Transplant Center After the First Wave of the COVID-19 Pandemic.
- 2021
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Ingår i: Transplantation. - 1534-6080. ; 105:1, s. 108-114
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Tidskriftsartikel (refereegranskat)abstract
- Solid organ transplant (SOT) recipients may be more vulnerable to coronavirus disease 2019 (COVID-19). Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the optimal management strategy for these patients is yet unclear.We present 53 SOT recipients (31 kidney transplant recipients, 8 liver transplant recipients, 5 heart transplant recipients, 5 lung transplant recipients, 3 liver-kidney transplant recipients, and 1 kidney-after-heart transplant recipient), transplanted at a Swedish high-volume transplant center and each diagnosed with COVID-19 between February 21, 2020 and June 22, 2020. Demographic, clinical, and treatment data were extracted from the electronic patient files.Patients reported fever (61%), cough (43%), diarrhea (31%), and upper respiratory symptoms (29%). The median age was 56 years, and 57% were male. According to severity, 55% had mild, 13% had moderate, 19% had severe, and 13% had critical disease. Thirty-seven patients (70%) were hospitalized, with 8 requiring intensive care. Thirteen of the 37 patients were initially managed as outpatients but later hospitalized. One patient received hydroxychloroquine, and no patients received antivirals. Antimetabolites and calcineurin inhibitors were held or reduced in two-thirds. Twenty-seven of 37 hospitalized patients (73%) received low-molecular-weight heparin. Five (13.5%) hospitalized patients died. Overall survival for the entire cohort was 90.5%. No rejection episodes were noted.Hospitalization, lowering of immunosuppression, and prophylactic anticoagulation were the most common therapeutic interventions for SOT recipients with COVID-19. A significant proportion of patients could be managed on an outpatient basis, while keeping a low threshold for admission. Mild and moderate disease forms seem to have a good outcome.
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| 30. |
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| 31. |
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| 32. |
- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 33. |
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| 34. |
- Gottlieb, J., et al.
(författare)
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Lung transplantation for acute respiratory distress syndrome: a retrospective European cohort study
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 59:6
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Tidskriftsartikel (refereegranskat)abstract
- Background The published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres. Methods We conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of "ARDS/pneumonia" were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed. Results 55 centres (81%) with a total transplant activity of 12438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015-2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977-55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation. Conclusions Lung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modem era. The selection process remains ethically and technically challenging.
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| 35. |
- Greer, M., et al.
(författare)
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Assessing treatment outcomes in CLAD: The Hannover-extracorporeal photopheresis model
- 2023
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 42:2, s. 209-217
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treat-ment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course. METHODS: Retrospective analysis of patients completing >= 3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were com-pared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation. RESULTS: Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photophe-resis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation. CONCLUSIONS: Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treat-ment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible. J Heart Lung Transplant 2023;42:209-217 (c) 2022 International Society for Heart and Lung Transplantation. All rights reserved.
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| 36. |
- Hammarström, Helena, et al.
(författare)
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Fungal Tracheobronchitis in Lung Transplant Recipients : Incidence and Utility of Diagnostic Markers
- 2023
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Ingår i: Journal of Fungi. - : MDPI AG. - 2309-608X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Fungal tracheobronchitis caused by Aspergillus and Candida spp. is a recognized complication after lung transplantation, but knowledge of the incidence of Candida tracheobronchitis is lacking. The diagnosis relies on fungal cultures in bronchoalveolar lavage fluid (BALF), but cultures have low specificity. We aimed to evaluate the one-year incidence of fungal tracheobronchitis after lung transplantation and to assess the utility of diagnostic markers in serum and BALF to discriminate fungal tracheobronchitis from colonization. Ninety-seven consecutively included adult lung-transplant recipients were prospectively followed. BALF and serum samples were collected at 1, 3 and 12 months after transplantation and analyzed for betaglucan (serum and BALF), neutrophils (BALF) and galactomannan (BALF). Fungal tracheobronchitis was defined according to consensus criteria, modified to include Candida as a mycologic criterion. The cumulative one-year incidence of Candida and Aspergillus tracheobronchitis was 23% and 16%, respectively. Neutrophils of >75% of total leukocytes in BALF had 92% specificity for Candida tracheobronchitis. The area under the ROC curves for betaglucan and galactomannan in BALF to discriminate Aspergillus tracheobronchitis from colonization or no fungal infection were high (0.86 (p < 0.0001) and 0.93 (p < 0.0001), respectively). To conclude, the one-year incidence of fungal tracheobronchitis after lung transplantation was high and dominated by Candida spp. Diagnostic markers in BALF could be useful to discriminate fungal colonization from tracheobronchitis.
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| 37. |
- Hoang, Oanh N, et al.
(författare)
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Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules.
- 2022
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Ingår i: American journal of respiratory and critical care medicine. - 1073-449X .- 1535-4970. ; 206:9, s. 1081-1095
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. Methods: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1β and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsy samples of transplanted lungs, and explanted lungs from subjects with chronic obstructive pulmonary disease. MUC5AC and MUC5B were labeled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins and imaged using widefield deconvolution or Airyscan fluorescence microscopy. Measurements and Main Results: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone. Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.
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| 38. |
- Hou, Yining, 1984-, et al.
(författare)
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Impact on voltage rise of PV generation in future swedish urban areas with high PV penetration
- 2014
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Ingår i: ENERGYCON 2014 - IEEE International Energy Conference. - : IEEE Computer Society. - 9781479924493 ; , s. 904-911
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Konferensbidrag (refereegranskat)abstract
- There have been a large amount of statements from different countries, claiming that the integration of photovoltaic generation in the distribution grids can eventually impact the power quality and pose challenges for the distribution system operator. In Sweden, the level of penetration of small scale distributed generation is still low and no such problems have been observed. This study is conducted to investigate the voltage levels in an urban distribution grid when the level of photovoltaic generation is increased. The study is done by modeling the Swedish urban area by PSCAD. The aspects of the model include network design of a real distribution grid, everyday load, photovoltaic generation based on real data, photovoltaic penetrations at different levels and considers the current regulations in Sweden. The results indicate that there are no problems with overvoltages even with a high penetration of photovoltaic generation. Instead the risk of over-current through the installed cables seems to be a greater limitation. The loading of the distribution transformers is decreased due to the mix of commercial and domestic loads in the local grid.
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| 39. |
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| 40. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 41. |
- Le Pavec, J. M., et al.
(författare)
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Lung transplantation for sarcoidosis: outcome and prognostic factors
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:2
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Tidskriftsartikel (refereegranskat)abstract
- Study question In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation. Patients and methods We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres. Results Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications. Answer to the study question Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.
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| 42. |
- Lindstrand, Anna, et al.
(författare)
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From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
- 2019
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Ingår i: Genome Medicine. - : BMC. - 1756-994X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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| 43. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 44. |
- Lund Hansen, Anders, et al.
(författare)
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Corona hotar förvärra svenska bostadskrisen : 108 forskare: Sveriges regering och kommuner måste förhindra en katastrof
- 2020
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DEBATE. Far from everyone who lives in Sweden has a secure housing situation. According to the National Board of Health and Welfare's latest national survey of 2017, there are about 33,000 homeless people in the country. A significant proportion of them are children. Due to the ongoing corona pandemic, many households are now threatened by unemployment and a deteriorating economy. If the state and municipalities do not act resolutely, there is an imminent risk that the housing crisis will deepen with devastating consequences for the individual as well as for society at large.
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| 45. |
- Magnusson, Jesper, et al.
(författare)
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A Retrospective Study of Posttransplant Amiodarone Exposition on Clad Development and Survival After Lung Transplantation.
- 2022
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 1873-2623 .- 0041-1345. ; 54:3, s. 789-794
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Tidskriftsartikel (refereegranskat)abstract
- Lung transplantation is a lifesaving procedure, still marred by worse results than other solid organ transplants. The 1-year mortality is 10%, and within 5 years after the procedure, half of patients develop chronic lung allograft dysfunction (CLAD), which also is the main limiting factor for long-term survival. Heart arrhythmias are also common directly after a lung transplant, and 1 treatment for this is the drug amiodarone. Recent research suggests that amiodarone exposure leads to activation of fibroblasts, a cell type that synthesizes stroma in the lung, associated with acute respiratory distress syndrome and CLAD. This study aims to retrospectively investigate the effect of posttransplant amiodarone treatment on survival and CLAD.All patients transplanted at Sahlgrenska University Hospital between 2007 and 2018 were reviewed, and adult patients with a follow-up within Sweden were included. Of the 394 patients who met this inclusion criteria, retrospective data concerning postoperative complications and long-term outcomes were retrieved. A multivariable Cox proportional hazards model was applied to identify a set of independently significant predictors.Posttransplant use of amiodarone was associated with shorter survival (hazard ratio=1.65; 95% confidence interval, 1.08-2.54; P=.02). Amiodarone exposure was not associated with CLAD (hazard ratio=0.64; 95% confidence interval, 0.33-1.22; P=.17).An increased risk of death but not CLAD was observed in patients treated with amiodarone postoperatively after lung transplantation in the current cohort.
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| 46. |
- Magnusson, Jesper, et al.
(författare)
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Broad and complex antifungal activity among environmental isolates of lactic acid bacteria
- 2003
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Ingår i: FEMS Microbiology Letters. - : Elsevier. - 0378-1097 .- 1574-6968. ; 219:1, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- More than 1200 isolates of lactic acid bacteria isolated from different environments were screened for antifungal activity in a dual-culture agar plate assay. Approximately 10% of the isolates showed inhibitory activity and 4% showed strong activity against the indicator mould Aspergillus fumigatus. The antifungal spectra for 37 isolates with strong activity and five isolates with low or no activity were determined. Several of the strains showed strong inhibitory activity against the moulds A. fumigatus, Aspergillus nidulans, Penicillium commune and Fusarium sporotrichioides, and also against the yeast Rhodotorula mucilaginosa. Penicillium roqueforti and the yeasts Pichia anomala and Kluyveromyces marxianus were not inhibited. Several isolates showed reduced antifungal activity after storage and handling. The majority of the fungal inhibitory isolates were identified by 16S rDNA sequencing as Lactobacillus coryniformis. Lactobacillus plantarum and Pediococcus pentosaceus were also frequently identified among the active isolates. The degree of fungal inhibition was not only related to production of lactic or acetic acid. In addition, antifungal cyclic dipeptides were identified after HPLC separation and several other active fractions were found suggesting a highly complex nature of the antifungal activity.
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| 47. |
- Magnusson, Jesper, et al.
(författare)
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Cell-free DNA as a biomarker after lung transplantation: A proof-of-concept study
- 2022
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Ingår i: Immunity Inflammation and Disease. - : Wiley. - 2050-4527. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD. Methods: Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events. Results: All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015). Conclusions: This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.
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| 48. |
- Magnusson, Jesper
(författare)
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Clustering Architectures: The Role of Materialities for Emerging Collectives in the Public Domain
- 2016. - 300
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is a study of social life, addressing issues concerning how and by what means people meet in urban public space. The main aim of this thesis is to is to investigate how certain artefacts and architectural features support the formation and temporal stabilisation of heterogeneous clusters and collectives, and thus, in order to the development of conceptual tools that can contribute to a more refined description and analysis of the role of architecture and artefacts for urban public life [a very long sentence…]. An important basis for this thesis is the conception of public life as an agglomeration of multiple, coexisting clusters of humans and nonhumans. Thus, urban public life can here be seen here as an effect of adding and losing parts of collectives – through the production and re-production of associations between human and nonhuman entities.The work has been carried out by the application and further development of concepts and methods mainly taken from territorology and actor-network theory (ANT). Affordance theory constitutes an additional theoretical approach that is included in the this thesis, however albeit to a less significant extent. Key questions related to the main objectives and the theoretical framework are for example: what What kind of competences, regarding territorial production and social exchange, can be associated to with material artefacts and to spatial configurations? Who and what constitutes actions and events that facilitate human co-existence in urban domains, ; i.e. how is urban public life produced?The empirical investigations consist of field studies of consumption spaces (open-air markets in London), leisure and play (playgrounds in Amsterdam) and spaces characterised by managed and curated activities (leisure spaces in Paris). The study sites were primarily selected because of their potential richness and diversity of socio-material exchanges. They also constitute intense gatherings of people, doing things together and individually, in close proximity of to fairly unknown others. The field study techniques employed in this thesis – guided by participant observation and photographic documentation – are mainly inspired by ‘visual ethnography’ as it is outlined by Sarah Pink and others, paired with public life studies executed by for example William H. Whyte and Jan Gehl.The studies explore how human interactions in urban spaces are dependent on networks that include artefacts, time, local policies and situated public cultures and practices. The main empirical findings were are successively conceptualised, tried in the empirical analysis and developed into a framework. The main themes – or actant categories – where materialities were found to be important for social interactions are: Anchors, Base Camps, Tickets and Rides; Monocore and Multitcore Spaces; Punctiform, Linear and Field Seating; and Ladders.These six actant categories, constituting the major outcomes of this thesis, can be seen as parts of a conceptual toolbox for investigating socio-material exchange and clustering in public domains. The conceptual tools suggest a particular attention to artefacts and architecture as significant social mediators, potentially facilitating encounters and exchanges between strangers. The actants are intended to supplement the terminology with which issues of social life in urban space are discussed and deconstructed. The actants are also intended to contribute more directly to planning and urban design practices, as operative tools, framing a relational, performative and processual approach to urban public domains.In this thesis, I have tried to show that the particular design and distribution of materialities in public domains have major strategic implications for questions regarding concerning co-existence, communality and collaboration. The proposed actants thus also represent an attempt to approach the challenges of segregation and polarisation through planning and urban design; not in an instrumental respect, or as recipes for a particular design concept, but as analytical keys that may support a more comprehensive understanding of actors and forces that profoundly affect social life in the public domain.
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| 49. |
- Magnusson, Jesper, et al.
(författare)
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COVID-19 in lung transplant recipients: an overview of the Swedish national experience.
- 2021
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 34:12, s. 2597-2608
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Tidskriftsartikel (refereegranskat)abstract
- Although it is known that solid organ transplant recipients fare worse after COVID-19 infection, data on the impact of COVID-19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow-up. In this nationwide study, all LTx recipients with COVID-19 diagnosed from 1 February 2020 to 30 April 2021 were included. The patients were followed until 1 August 2021 or death. We analysed demographics, clinical features, therapeutic management and outcomes, including lung function. Forty-seven patients were identified: median age was 59 (10-78) years, 53.1% were male, and median follow-up was 194 (23-509) days. COVID-19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre-COVID infection. Two patients (4.3%) died within 28days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (P=0.004). LTx recipients develop the entire spectrum of COVID-19, and in addition to previously acknowledged risk factors, lower pre-COVID lung function was associated with more severe disease presentation.
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| 50. |
- Magnusson, Jesper, 1984-, et al.
(författare)
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Design Aspects of a Medium Voltage Hybrid DC Breaker
- 2014
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Ingår i: 5th IEEE/PES Innovative Smart Grid Technologies Europe (ISGT EUROPE) 2014.
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Konferensbidrag (refereegranskat)abstract
- With increased demands on energy efficiency and stability, the use of direct current (DC) will have a natural place in the future smart grid. Today DC is mostly used in high voltage, high power transmission over large distances and in low voltage systems where the demands on reliability are high, e.g. data centres. New applications as wind farm collection grids and a desire to replace over-head lines with cables opens possibilities for DC distribution grids in medium voltage.The use of DC grids will require the development of DC breakers to handle fault in the grid. This paper presents the design aspects of a hybrid DC breaker for a medium voltage application. Since the hybrid topology consists of a mechanical switch as well as semiconductor components and metal oxide varistors, the design must handle trade-offs in performance and cost both for each part and also between the different components.
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