| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- Fekete, Sandor P., et al.
(författare)
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Computing Nonsimple Polygons of Minimum Perimeter
- 2016
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Ingår i: EXPERIMENTAL ALGORITHMS, SEA 2016. - Cham : SPRINGER INT PUBLISHING AG. - 9783319388502 - 9783319388519 ; , s. 134-149
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Konferensbidrag (refereegranskat)abstract
- We provide exact and approximation methods for solving a geometric relaxation of the Traveling Salesman Problem (TSP) that occurs in curve reconstruction: for a given set of vertices in the plane, the problem Minimum Perimeter Polygon (MPP) asks for a (not necessarily simply connected) polygon with shortest possible boundary length. Even though the closely related problem of finding a minimum cycle cover is polynomially solvable by matching techniques, we prove how the topological structure of a polygon leads to NP-hardness of the MPP. On the positive side, we show how to achieve a constant-factor approximation. When trying to solve MPP instances to provable optimality by means of integer programming, an additional difficulty compared to the TSP is the fact that only a subset of subtour constraints is valid, depending not on combinatorics, but on geometry. We overcome this difficulty by establishing and exploiting additional geometric properties. This allows us to reliably solve a wide range of benchmark instances with up to 600 vertices within reasonable time on a standard machine. We also show that using a natural geometry-based sparsification yields results that are on average within 0.5% of the optimum.
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| 3. |
- Fekete, Sándor P., et al.
(författare)
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Computing Nonsimple Polygons of Minimum Perimeter
- 2017
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Ingår i: Journal of Computational Geometry. - Ottawa, Canada : Carleton University * Department of Mathematics and Statistics. - 1920-180X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We consider the Minimum Perimeter Polygon Problem (MP3): for a given set V of points in the plane, find a polygon P with holes that has vertex set V , such that the total boundary length is smallest possible. The MP3 can be considered a natural geometric generalization of the Traveling Salesman Problem (TSP), which asks for a simple polygon with minimum perimeter. Just like the TSP, the MP3 occurs naturally in the context of curve reconstruction. Even though the closely related problem of finding a minimum cycle cover is polynomially solvable by matching techniques, we prove how the topological structure of a polygon leads to NP-hardness of the MP3. On the positive side, we provide constant-factor approximation algorithms. In addition to algorithms with theoretical worst-case guarantess, we provide practical methods for computing provably optimal solutions for relatively large instances, based on integer programming. An additional difficulty compared to the TSP is the fact that only a subset of subtour constraints is valid, depending not on combinatorics, but on geometry. We overcome this difficulty by establishing and exploiting geometric properties. This allows us to reliably solve a wide range of benchmark instances with up to 600 vertices within reasonable time on a standard machine. We also show that restricting the set of connections between points to edges of the Delaunay triangulation yields results that are on average within 0.5% of the optimum for large classes of benchmark instances.
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| 4. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 5. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 6. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 7. |
- Aichholzer, Oswin, et al.
(författare)
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Folding Polyominoes into (Poly)Cubes
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Ingår i: International journal of computational geometry and applications. - 0218-1959.
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 9. |
- Aichholzer, Oswin, et al.
(författare)
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Folding Polyominoes with Holes into a Cube
- 2021
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Ingår i: Computational geometry. - : Elsevier. - 0925-7721 .- 1879-081X. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special “basic” holes guarantee foldability.
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| 10. |
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| 11. |
- Alegría, Carlos, et al.
(författare)
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The Complexity of the Lower Envelope of Collections of Various Geometric Shapes
- 2024
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Ingår i: 40th European Workshop on Computational Geometry. ; , s. 200-206
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Konferensbidrag (refereegranskat)abstract
- We study the problem of determining the complexity of the lower envelope of a collection of n geometric objects. For collections of rays; unit length line segments; and collections of unit squares to which we apply at most two transformations from translation, rotation, and scaling, we prove a complexity of Θ(n). If all three transformations are applied to unit squares, then we show the complexity becomes Θ(nα(n)), where α(n) is the slowly growing inverse of Ackermann’s function.
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| 12. |
- Andersson Granberg, Tobias, et al.
(författare)
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A framework for integrated terminal airspace design
- 2019
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Ingår i: Aeronautical Journal. - : CAMBRIDGE UNIV PRESS. - 0001-9240 .- 2059-6464. ; 123:1263, s. 567-585
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Tidskriftsartikel (refereegranskat)abstract
- Route planning and airspace sectorisation are two central tasks in air traffic management. Traditionally, the routing and sectorisation problems were considered separately, with aircraft trajectories serving as input to the sectorisation problem and, reciprocally, sectors being part of the input to the path finding algorithms. In this paper we propose a simultaneous design of routes and sectors for a transition airspace. We compare two approaches for this integrated design: one based on mixed integer programming, and one Voronoi-based model that separates potential "hotspots" of controller activity resulting from the terminal routes. We apply our two approaches to the design of Stockholm Terminal Maneuvering Area.
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| 13. |
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| 14. |
- Andersson Granberg, Tobias, et al.
(författare)
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A Novel MIP-based Airspace Sectorization for TMAs
- 2017
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Ingår i: 12th USA/Europe Air Traffic Management R and D Seminar. - : EUROCONTROL.
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Konferensbidrag (refereegranskat)abstract
- We present a MIP-based airspace sectorization framework for Terminal Maneuvering Areas (TMAs). It incorporates an airspace complexity representation, as well as various constraints on the sectors' geometry, e.g., the requirement that points that demand increased attention from air traffic controllers should lie in the sector's interior to allow for enough time to resolve possible conflicts. In contrast to earlier integer/constraint programming approaches, which used synthesis methods with variables per elementary airspace piece that were glued together to form sectors, our IP formulation uses a variable per potential edge on the sector boundary. It is also the first step towards an integrated design of routes, the resulting complexity, and a sectorization. We present results for Stockholm TMA.
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| 15. |
- Andersson Granberg, Tobias, et al.
(författare)
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Automatic Design of Aircraft Arrival Routes with Limited Turning Angle
- 2016
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Ingår i: 16th Workshop on Algorithmic Approaches for Transportation Modelling, Optimization, and Systems (ATMOS 2016). - Dagstuhl, Germany. - 9783959770217 ; , s. 9:1-9:13
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Konferensbidrag (refereegranskat)abstract
- We present an application of Integer Programming to the design of arrival routes for aircraft in a Terminal Maneuvering Area (TMA). We generate operationally feasible merge trees of curvature-constrained routes, using two optimization criteria: (1) total length of the tree, and (2) distance flown along the tree paths. The output routes guarantee that the overall traffic pattern in the TMA can be monitored by air traffic controllers; in particular, we keep merge points for arriving aircraft well separated, and we exclude conflicts between arriving and departing aircraft. We demonstrate the feasibility of our method by experimenting with arrival routes for a runway at Arlanda airport in the Stockholm TMA. Our approach can easily be extended in several ways, e.g., to ensure that the routes avoid no-fly zones.
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| 16. |
- Andersson Granberg, Tobias, 1973-, et al.
(författare)
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Configuration and Planning of the Remote TowerModules in a Remote Tower Center
- 2016
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Konferensbidrag (refereegranskat)abstract
- Today, many small aerodromes struggle withfinancial difficulties, and a large cost is air traffic control.Remote tower centers, which remotely provide air traffic servicesto aerodromes, can help reduce this cost. Each center maycontain a number of remote tower modules, where each moduleis manned by a controller that can handle one or moreaerodromes. In this paper we present the remote tower centerconcept and develop a model that optimizes the assignment ofairports to the remote tower modules. Computational results fora possible scenario based on real data for Swedish airports arepresented.
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| 17. |
- Andersson Granberg, Tobias, 1973-, et al.
(författare)
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Integer Programming-Based Airspace Sectorization for Terminal Maneuvering Areas with Convex Sectors
- 2019
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Ingår i: Journal of Air Transportation. - : American Institute of Aeronautics and Astronautics. - 2380-9450. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- In this paper an airspace sectorization framework for terminal maneuvering areas based on mixed integer programming is presented. It incorporates an airspace complexity representation, as well as various constraints on the sectors’ geometry, for example, the requirement that points demanding increased attention from air traffic controllers should lie in the sector’s interior to allow for enough time to resolve possible conflicts. The method can enforce convex sectors. In contrast to earlier integer/constraint programming approaches, which used synthesis methods with variables per elementary airspace piece that were glued together to form sectors, the integer programming formulation uses a variable per potential edge on the sector boundary. It is also the first step toward an integrated design of routes, the resulting complexity, and a sectorization. This paper presents results for Stockholm Arlanda airport and compares the integer programming results to convex sectorizations obtained by enumerating all possible topologies for a given number of sectors. This yields a proof-of-concept for the application of this highly flexible approach to terminal maneuvering areas.
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| 18. |
- Anna, Brötzner, et al.
(författare)
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The k-Transmitter Watchman Route Problem is NP-Hard Even in Histograms and Star-Shaped Polygons
- 2024
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Ingår i: 40th European Workshop on Computational Geometry. ; , s. 381-387
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Konferensbidrag (refereegranskat)abstract
- A k-transmitter g in a polygon P, with n vertices, k-sees a point p ∈ P if the line segment gp intersects P’s boundary at most k times. In the k-Transmitter Watchman Route Problem we aim to minimize the length of a k-transmitter watchman route along which every point in the polygon—or a discrete set of points in the interior of the polygon—is k-seen. We show that the k-Transmitter Watchman Route Problem for a discrete set of points is NP-hard for histograms, uni-monotone polygons, and star-shaped polygons given a fixed starting point. For histograms and uni-monotone polygons it is also NP-hard without a fixed starting point. Moreover, none of these versions can be approximated to within a factor c · log n, for any constant c > 0.
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| 19. |
- Bagheri, Alireza, et al.
(författare)
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Minsum m watchmen’s routes in Stiegl polygons
- 2023
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Ingår i: XX Spanish Meeting on Computational Geometry. ; , s. 41-44
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Konferensbidrag (refereegranskat)abstract
- We present an O(n2 · min{m, n}) time and O(n · min{m, n}) storage algorithm to compute the minsum set of m watchmen routes given their starting points in a Stiegl polygon ― a staircase polygon where the floor solely consists of one horizontal and one vertical edge ― with n vertices.
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| 20. |
- Burke, Kyle, et al.
(författare)
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Single-Player and Two-Player Buttons & Scissors Games
- 2016
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Ingår i: DISCRETE AND COMPUTATIONAL GEOMETRY AND GRAPHS, JCDCGG 2015. - Cham : SPRINGER INT PUBLISHING AG. - 9783319485324 - 9783319485317 ; , s. 60-72
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Konferensbidrag (refereegranskat)abstract
- We study the computational complexity of the Buttons amp; Scissors game and obtain sharp thresholds with respect to several parameters. Specifically we show that the game is NP-complete for C = 2 colors but polytime solvable for C = 1. Similarly the game is NP-complete if every color is used by at most F = 4 buttons but polytime solvable for F amp;lt;= 3. We also consider restrictions on the board size, cut directions, and cut sizes. Finally, we introduce several natural two-player versions of the game and show that they are PSPACE-complete.
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| 21. |
- Cannon, Sarah, et al.
(författare)
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Combinatorics and complexity of guarding polygons with edge and point 2-transmitters
- 2018
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Ingår i: Computational geometry. - : Elsevier. - 0925-7721 .- 1879-081X. ; 68, s. 89-100
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Tidskriftsartikel (refereegranskat)abstract
- We consider a generalization of the classical Art Gallery Problem, where instead of a light source, the guards, called k-transmitters, model a wireless device with a signal that can pass through at most k walls. We show it is NP-hard to compute a minimum cover of point 2-transmitters, point k-transmitters, and edge 2-transmitters in a simple polygon. The point 2-transmitter result extends to orthogonal polygons. In addition, we give necessity and sufficiency results for the number of edge 2-transmitters in general, monotone, orthogonal monotone, and orthogonal polygons.
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| 22. |
- Daescu, Ovidiu, et al.
(författare)
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Altitude Terrain Guarding and Guarding Uni-Monotone Polygons
- 2019
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Ingår i: Computational geometry. - : Elsevier. - 0925-7721 .- 1879-081X. ; 84, s. 22-35
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Tidskriftsartikel (refereegranskat)abstract
- We present an optimal, linear-time algorithm for the following version of terrain guarding: given a 1.5D terrain and a horizontal line, place the minimum number of guards on the line to see all of the terrain. We prove that the cardinality of the minimum guard set coincides with the cardinality of a maximum number of “witnesses”, i.e., terrain points, no two of which can be seen by a single guard. We show that our results also apply to the Art Gallery problem in “monotone mountains”, i.e., x-monotone polygons with a single edge as one of the boundary chains. This means that any monotone mountain is “perfect” (its guarding number is the same as its witness number); we thus establish the first non-trivial class of perfect polygons.
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| 23. |
- Dahlberg, Joen, et al.
(författare)
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Capacity-Driven Automatic Design of Dynamic Aircraft Arrival Routes
- 2018
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Ingår i: 2018 IEEE/AIAA 37TH DIGITAL AVIONICS SYSTEMS CONFERENCE (DASC). - : IEEE. - 9781538641125 ; , s. 1194-1202
-
Konferensbidrag (refereegranskat)abstract
- We present a Mixed-Integer Programming framework for the design of aircraft arrival routes in a Terminal Maneuvering Area (TMA) that guarantee temporal separation of aircraft. The output routes constitute operationally feasible merge trees, and guarantee that the overall traffic pattern in the TMA can be monitored by air traffic controllers; in particular, we ensure that all aircraft on the arrival routes are separated in time and all merge points are spatially separated. We present a proof of concept of our approach, and demonstrate its feasibility by experiments for arrival routes during one hour at Stockholm TMA.
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| 24. |
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| 25. |
- Demaine, Erik D., et al.
(författare)
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Rectangular Spiral Galaxies are still hard
- 2023
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Ingår i: Computational geometry. - : Elsevier. - 0925-7721 .- 1879-081X. ; 110
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Tidskriftsartikel (refereegranskat)abstract
- Spiral Galaxies is a pencil-and-paper puzzle played on a grid of unit squares: given a set of points called centers, the goal is to partition the grid into polyominoes such that each polyomino contains exactly one center and is 180 degrees rotationally symmetric about its center. We show that this puzzle is NP-complete, ASP-complete, and #P-complete even if (a) all solutions to the puzzle have rectangles for polyominoes; or (b) the polyominoes are required to be rectangles and all solutions to the puzzle have just 1 x 1, 1 x 3, and 3 x 1 rectangles. The proof for the latter variant also implies NP/ASP/#P-completeness of finding a noncrossing perfect matching in distance-2 grid graphs where edges connect vertices of Euclidean distance 2. Moreover, we prove NP-completeness of the design problem of minimizing the number of centers such that there exists a set of galaxies that exactly cover a given shape.(c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 26. |
- Dreyling, Martin, et al.
(författare)
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Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE) : a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
- 2024
-
Ingår i: The Lancet. - 0140-6736. ; 403:10441, s. 2293-2306
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.
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| 27. |
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| 28. |
- Erlandson, William, et al.
(författare)
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Meta-Heuristic for inserting a robust train path in a non-cyclic timetable
- 2023
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Ingår i: Transportation planning and technology (Print). - : TAYLOR & FRANCIS LTD. - 0308-1060 .- 1029-0354. ; 46:7, s. 842-863
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Tidskriftsartikel (refereegranskat)abstract
- Many freight trains depart Swedish marshalling yards before or after their planned departure times. Today, a deviating departure time is allowed if no conflicting train path can be found a few stations ahead. This increases the risk that the train might be delayed to its destination and cause delays to other trains. We present a meta-heuristic that modifies a timetable by adding a train path (for our freight train) and, if necessary, adjusting surrounding train paths. The aim of the insertion of the additional train path and the adjustments of the existing ones is to obtain a large bottleneck robustness, that is, the largest possible minimal temporal distance to any other train in the timetable. We provide experimental results for a Swedish railway stretch with a non-cyclic timetable and heterogeneous traffic. We show that we quickly add a train path, while improving the robustness of the timetable.
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| 29. |
- Ernestus, Maximilian, et al.
(författare)
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Algorithms for art gallery illumination
- 2017
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Ingår i: Journal of Global Optimization. - : SPRINGER. - 0925-5001 .- 1573-2916. ; 68:1, s. 23-45
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Tidskriftsartikel (refereegranskat)abstract
- The art gallery problem (AGP) is one of the classical problems in computational geometry. It asks for the minimum number of guards required to achieve visibility coverage of a given polygon. The AGP is well-known to be NP-hard even in restricted cases. In this paper, we consider the AGP with fading (AGPF): A polygonal region is to be illuminated with light sources such that every point is illuminated with at least a global threshold, light intensity decreases over distance, and we seek to minimize the total energy consumption. Choosing fading exponents of zero, one, and two are equivalent to the AGP, laser scanner applications, and natural light, respectively. We present complexity results as well as a negative solvability result. Still, we propose two practical algorithms for AGPF with fixed light positions (e.g. vertex guards) independent of the fading exponent, which we demonstrate to work well in practice. One is based on a discrete approximation, the other on non-linear programming by means of simplex-partitioning strategies. The former approach yields a fully polynomial-time approximation scheme for the AGPF with fixed light positions. The latter approach obtains better results in our experimental evaluation.
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| 30. |
- Filtser, Omrit, et al.
(författare)
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Guarding Polyominoes Under k-Hop Visibility
- 2024
-
Ingår i: LATIN 2024. - : Springer Publishing Company. - 9783031555978 - 9783031555985 ; , s. 288-302
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Konferensbidrag (refereegranskat)abstract
- We study the ART GALLERY Problem under k-hop visibility in polyominoes. In this visibility model, two unit squares of a polyomino can see each other if and only if the shortest path between the respective vertices in the dual graph of the polyomino has length at most k. In this paper, we show that the VC dimension of this problem is 3 in simple polyominoes, and 4 in polyominoes with holes. Furthermore, we provide a reduction from PLANAR MONOTONE 3SAT, thereby showing that the problem is NP-complete even in thin polyominoes (i.e., polyominoes that do not a contain a 2 x 2 block of cells). Complementarily, we present a linear-time 4-approximation algorithm for simple 2-thin polyominoes (which do not contain a 3 x 3 block of cells) for all k is an element of N.
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| 31. |
- Friedrichs, Stephan, et al.
(författare)
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The continuous 1.5D terrain guarding problem: Discretization, optimal solutions, and PTAS
- 2016
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Ingår i: Journal of Computational Geometry. - : Carleton University. - 1920-180X. ; 7:1, s. 256-284
-
Tidskriftsartikel (refereegranskat)abstract
- In the NP-hard continuous 1.5D Terrain Guarding Problem (TGP) we are given an xx-monotone chain of line segments in R2 (the terrain TT), and ask for the minimum number of guards (located anywhere on TT) required to guard all of TT. We construct guard candidate and witness sets G,W⊂T of polynomial size such that any feasible (optimal) guard cover G∗⊆Gfor WW is also feasible (optimal) for the continuous TGP. This discretization allows us to: (1) settle NP-completeness for the continuous TGP; (2) provide a Polynomial Time Approximation Scheme (PTAS) for the continuous TGP using the PTAS for the discrete TGP by Gibson et al.; (3) formulate the continuous TGP as an Integer Linear Program (IP). Furthermore, we propose several filtering techniques reducing the size of our discretization, allowing us to devise an efficient IP-based algorithm that reliably provides optimal guard placements for terrains with up to 10^6 vertices within minutes on a standard desktop computer.
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| 32. |
- Frykholm, Peter, 1961-, et al.
(författare)
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Pre-operative fasting in children : A guideline from the European Society of Anaesthesiology and Intensive Care
- 2022
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Ingår i: European Journal of Anaesthesiology. - : European Society of Anaesthesiology and Intensive Care. - 0265-0215 .- 1365-2346. ; 39:1, s. 4-25
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Tidskriftsartikel (refereegranskat)abstract
- Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents.We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force.Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a ‘light breakfast’ may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying.
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| 33. |
- Hajizadeh, Roghayeh, 1986-, et al.
(författare)
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A Dantzig-Wolfe Reformulation for AutomatedAircraft Arrival Scheduling in TMAs
- 2024
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Ingår i: Proceedings of the 14th International Conference on the Practice and Theory of Automated Timetabling, PATAT 2024. - 9780992998462 ; , s. 268-271
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Konferensbidrag (refereegranskat)abstract
- In this paper, we introduce a Dantzig-Wolfe reformulation to compute aircraft arrival routes in a terminal maneuvering area (TMA) where the aircraft are flying according to theoptimal continuous-descent-operation (CDO) speed profile with idle thrust. This model assumes fixed entry times for all aircraft and a single separation time that is independent of wake-turbulence categories.Preliminary experiments show that this approach leads to significantly reduced runtimes.Moreover, the results indicate the possiblity of extending the reformulation to the full model and applying it to address additional practical considerations, such as wind effects in the future.
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| 34. |
- Hernández Romero, Eulalia, et al.
(författare)
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Integrating weather impact in air traffic controller shift scheduling in remote and conventional towers
- 2022
-
Ingår i: EURO Journal on Transportation and Logistics. - : Elsevier. - 2192-4376 .- 2192-4384. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Weather affects the work of air traffic controllers, however, for staff scheduling in Remote Tower Centers (RTCs) it has not been taken into account. We study the impact of various weather phenomena on air traffic controller (ATCO) taskload through structured interviews with ATCOs. We deduce taskload-driven impact factors and the corresponding thresholds for the intensity of the weather phenomena at several Swedish airports. To account for the uncertainty in the weather prediction, we obtain probabilistic weather data from Ensemble Prediction Systems (EPSs). Then we adjust our prior Mixed Integer Programming (MIP) model for RTC staff scheduling to account for uncertain impactful weather occurrences and yield a distribution for the necessary number of ATCOs for RTC staff scheduling. Our framework can be used for conventional towers as well. We quantify the impact of weather by comparing the number of controllers necessary to operate at five Swedish airports from a remote tower during two example days in 2020, with and without taking weather events into account. In our calculations we use historical weather and flight data to show that ignoring weather impact may lead to significant understaffing at a RTC.
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| 35. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 36. |
- Hopp, Sarah, et al.
(författare)
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Targeting Coagulation Factor XII as a Novel Therapeutic Option in Brain Trauma
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 970-982
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury.Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury.Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage.Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.
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| 37. |
- Josefsson, Billy, et al.
(författare)
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A Step Towards Remote Tower Center Deployment: Optimizing Staff Scheduling
- 2017
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Ingår i: 11th USA/Europe Air Traffic Management Research and Development Seminar 2015. - : The European Organisation for the Safety of Air Navigation. - 9781510810402
-
Konferensbidrag (refereegranskat)abstract
- —Remote Tower Service (RTSs) is one of the technological and operational solutions delivered for deployment by the Single European Sky ATM Research (SESAR) Programme. This new concept fundamentally changes how operators provide Air Traffic Services, as it becomes possible to control several airports from a single remote center. In such settings an air traffic controller works at a so-called “multiple position” in the remote center, that is, he/she handles two or more airports from one Remote Tower Module (RTM), i.e the controller working position. In this paper, we present an optimization framework for the traffic management at five Swedish airports that were chosen for remote operation using a Remote Tower Center designed to serve a number of airports. We highlight the problems experienced with real airport schedules, and present optimal assignments of the airports to the RTMs. We consider both scheduled traffic and special (non-scheduled) traffic at these five airports.
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| 38. |
- Josefsson, Billy, et al.
(författare)
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A Step Towards Remote Tower Center Deployment: Optimizing Staff Scheduling
- 2019
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Ingår i: Journal of Air Transportation. - : American Institute of Aeronautics and Astronautics. - 2380-9450. ; 27:3
-
Tidskriftsartikel (refereegranskat)abstract
- Remote tower service is one of the technological and operational solutions delivered for deployment by the Single European Sky Air Traffic Management Research Program. This new concept fundamentally changes how operators provide air traffic services as it becomes possible to control several airports from a single remote center. In such settings, an air traffic controller works at a so-called multiple position in the remote center; that is, he/she handles two or more airports from one remote tower module, that is, the controller working position. In this paper, an optimization framework is presented for traffic management at five Swedish airports that were chosen for remote operation using a remote tower center designed to serve a number of airports. The problems experienced with real airport schedules are highlighted, and optimal assignments of the airports to the remote tower modules are presented. Both scheduled traffic and special (nonscheduled) traffic at these five airports are considered.
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| 39. |
- Josefsson, Billy, et al.
(författare)
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Identification of Complexity Factors for Remote Towers
- 2018
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Ingår i: SESAR Innovation Days. - : SESAR Joint Undertaking.
-
Konferensbidrag (refereegranskat)abstract
- An implementation of the Remote Tower concept comes with the challenge of optimizing staff resources subject to safety requirements. To distinguish safe from unsafe assignments, the quantification of tower controller workload—which is not a new problem—needs to be reconsidered in the setting of a remote tower environment. We plan to identify the remote operation specific complexity factors, which will be the basis of finding measures that have a high correlation to these factors that together describe the workload. In this paper, we analyze simulation data for these complexity factors. In the simulation different controllers rated the workload while monitoring multiple airports (either with simultaneously visible screens, or switching between the displays). We focus on complexity factors that stem from the interplay of Tower and Ground Control. The resulting list of the most significant complexity factors gives a base for our future quantification of remote tower controller workload. © 2018, SESAR Joint Undertaking. All rights reserved.
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| 40. |
- Josefsson, Billy, et al.
(författare)
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Scheduling Air Traffic Controllers at the Remote Tower Center
- 2017
-
Ingår i: Digital Avionics Systems Conference (DASC), 2017 IEEE/AIAA 36th. - : IEEE. - 9781538603659 - 9781538603666
-
Konferensbidrag (refereegranskat)abstract
- Remote Tower Service (RTS) is one of the technological and operational solutions delivered for deployment by the Single European Sky ATM Research (SESAR) Programme. This new concept fundamentally changes how operators provide Air Traffic Services, as it becomes possible to control several airports from a single remote center. In such settings an air traffic controller works at a so-called “multiple position” at the Remote Tower Center (RTC), which means that he/she can handle two or more airports from one Remote Tower Module (controller working position). In this paper, we present an optimization framework designed for automation of staff planning at the RTC. We highlight the problems experienced with real airport flight schedules, and present optimal shift assignments for five Swedish airports that were chosen for remote operation.
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| 41. |
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| 42. |
- 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
-
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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| 43. |
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| 44. |
- Krohn, Erik, et al.
(författare)
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Opposing Half Guards
- 2022
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Ingår i: 34th Canadian Conference on Computational Geometry. - : Canadian Conference on Computational Geometry. ; , s. 219-226
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Konferensbidrag (refereegranskat)abstract
- We study the art gallery problem for opposing halfguards: guards that can either see to their left or to theirright only. We present art gallery theorems, show thatthe problem is NP-hard in monotone polygons, presentapproximation algorithms for spiral and staircase poly-gons, and show that the location of half guards in 2-guardable polygons is not restricted to extensions.
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| 45. |
- LeKieffre, Charlotte, et al.
(författare)
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Ammonium and Sulfate Assimilation Is Widespread in Benthic Foraminifera
- 2022
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Nitrogen and sulfur are key elements in the biogeochemical cycles of marine ecosystems to which benthic foraminifera contribute significantly. Yet, cell-specific assimilation of ammonium, nitrate and sulfate by these protists is poorly characterized and understood across their wide range of species-specific trophic strategies. For example, detailed knowledge about ammonium and sulfate assimilation pathways is lacking and although some benthic foraminifera are known to maintain intracellular pools of nitrate and/or to denitrify, the potential use of nitrate-derived nitrogen for anabolic processes has not been systematically studied. In the present study, NanoSIMS isotopic imaging correlated with transmission electron microscopy was used to trace the incorporation of isotopically labeled inorganic nitrogen (ammonium or nitrate) and sulfate into the biomass of twelve benthic foraminiferal species from different marine environments. On timescales of twenty hours, no detectable 15N-enrichments from nitrate assimilation were observed in species known to perform denitrification, indicating that, while denitrifying foraminifera store intra-cellular nitrate, they do not use nitrate-derived nitrogen to build their biomass. Assimilation of both ammonium and sulfate, with corresponding 15N and 34S-enrichments, were observed in all species investigated (with some individual exceptions for sulfate). Assimilation of ammonium and sulfate thus can be considered widespread among benthic foraminifera. These metabolic capacities may help to underpin the ability of benthic foraminifera to colonize highly diverse marine habitats.
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| 46. |
- Lemetti, Anastasia, et al.
(författare)
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Discrete-Fourier-Transform-Based Evaluation of Physiological Measures as Workload Indicators
- 2023
-
Ingår i: 2023 IEEE/AIAA 42ND DIGITAL AVIONICS SYSTEMS CONFERENCE, DASC. - : IEEE. - 9798350333572 - 9798350333589
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Konferensbidrag (refereegranskat)abstract
- We propose a new approach to evaluate ocular measurements of air traffic controllers (ATCOs) as potential workload and fatigue indicators. We employ the Fast Fourier transform (FFT) to test our assumption that humans respond to increasing fatigue with harmonic oscillations in the eye movement, while they respond to increasingly high workload with disruptions to these harmonic oscillations. The FFT yields the frequency spectrum and we suggest to use the center of gravity of this spectrum to capture the variations. We give a proof-of concept study to evaluate our approach and we were able to verify our hypotheses in some cases, in particular, we identify the fixation duration as a promising indicator of changes in workload.
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| 47. |
- Lidén, Tomas, et al.
(författare)
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Improving attractiveness of working shifts for train dispatchers
- 2024
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Ingår i: Transportmetrica B. - : TAYLOR & FRANCIS LTD. - 2168-0566. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- We consider the problem of scheduling shifts for train dispatchers: given legal and operational constraints, the dispatching work in geographical areas should be assigned to dispatchers. In previous work, we presented an integer-programming framework for scheduling one-day shifts, aiming to minimize the number of dispatchers needed. Here, we present a stronger formulation for this problem. Moreover, we handle several quality aspects of the resulting shifts: we exclude undesirable start times and too short shifts; and we present four approaches to handle unnecessary changes in the dispatcher-area assignments. With an experimental performance-evaluation, we show that the stronger model significantly reduces the runtime in all but one instance, with an average decrease of 82.2 percent. We can solve all real-world-sized instances in less than 10 seconds. Moreover, we compare the four handover-approaches on instances with different temporal and geographical resolutions, and show that the two promising approaches allow us to solve a real-world-sized instance.
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| 48. |
- Ljunggren, Fredrik, et al.
(författare)
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Maximum Robust Train Path for an Additional Train Inserted in an Existing Railway Timetable
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present an algorithm to insert a train path in an existing railway timetable close to operation, when we want to affect the existing (passenger) traffic as little as possible. Thus, we consider all other trains as fixed, and aim for a resulting train path that maximizes the bottleneck robustness. Our algorithm is based on a graph formulation of the problem and uses a variant of Dijkstra's algorithm.We present an extensive experimental evaluation of our algorithm for the Swedish railway stretch from Malmö to Hallsberg. Moreover, we analyze the size of our constructed graph.
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| 49. |
- Ljunggren, Fredrik, et al.
(författare)
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Railway timetabling : a maximum bottleneck path algorithm for finding an additional train path
- 2021
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Ingår i: Public Transport. - : Springer. - 1866-749X .- 1613-7159. ; 13, s. 597-623
-
Tidskriftsartikel (refereegranskat)abstract
- We present an algorithm to insert a train path in an existing railway timetable close to operation, when we want to affect the existing (passenger) traffic as little as possible. Thus, we consider all other trains as fixed, and aim for a resulting train path that maximizes the bottleneck robustness, that is, a train path that maximizes the temporal distance to neighboring trains in the timetable. Our algorithm is based on a graph formulation of the problem and uses a variant of Dijkstra’s algorithm. We present an extensive experimental evaluation of our algorithm for the Swedish railway stretch from Malmö to Hallsberg. Moreover, we analyze the size of our constructed graph.
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| 50. |
- Mannes, Marco, et al.
(författare)
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Combined Heterozygous Genetic Variations in Complement C2 and C8B : An Explanation for Multidimensional Immune Imbalance?
- 2023
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Ingår i: Journal of Innate Immunity. - : S. Karger. - 1662-811X .- 1662-8128. ; 15:1, s. 412-427
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625C>T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. While no autoimmune disease-specific autoantibodies could be detected, genetic analysis revealed abnormalities in the two complement genes C2 and C8B. Therefore, we performed a comprehensive investigation of the innate immune system on a cellular and humoral level to define the functional consequences. We found slightly impaired functionality of neutrophils and monocytes regarding phagocytosis and reactive oxygen species generation and a diminished expression of the C5aR1. An extensive complement analysis revealed a declined activation potential for the alternative and classical pathway. Reconstitution with purified C2 and C8 into patient serum failed to normalize the dysfunction, whereas the addition of C3 improved the hemolytic activity. In clinical transfer, in vitro supplementation of the patient's plasma with FFP as a complement source could fully restore full complement functionality. This study describes for the first time a combined heterozygous genetic variation in complement C2 and C8B which, however, cannot fully explain the overall dysfunctions and calls for further complement deficiency research and corresponding therapies.
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