| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Pelletier, F., et al.
(författare)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 3. |
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| 4. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 5. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 6. |
- Went, M, et al.
(författare)
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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3707-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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| 7. |
- Aleksandrov, D., et al.
(författare)
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Invariant mass spectrum and alpha-n correlation function studied in the fragmentation of He-6 on a carbon target
- 1998
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Ingår i: Nuclear Physics A. - 0375-9474. ; 633:2, s. 234-246
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Tidskriftsartikel (refereegranskat)abstract
- Momentum distributions and invariant mass spectra from the breakup of He-6 ions with an energy of 240 MeV/u interacting with a carbon target have been studied. The data were used to extract information about the reaction mechanism which is influenced by the structure of He-6. It is found that the dominant reaction mechanism is a two-step process: knock out of one neutron followed by the decay of the He-5 resonance. The shape of the (alpha+n) two-body invariant mass spectrum is interpreted as mainly reflecting the 5He ground state which is a J(pi) = 3/2(-) resonance. However, no evidence for correlations between cu particles and neutrons is observed in the momentum widths of the distributions. It is demonstrated that a combined analysis of the two-body invariant mass spectrum and an appropriate correlation function may be used to determine the properties of the intermediate resonance. (C) 1998 Elsevier Science B.V.
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| 8. |
- Chulkov, L. V., et al.
(författare)
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Large spin alignment of the unbound He-5 fragment after fragmentation of 240 MeV/nucleon He-6
- 1997
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 79:2, s. 201-204
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral fragmentation of a 240 MeV/nucleon beam of the halo nucleus He-6 incident on carbon target has been studied in a kinematically complete experiment. It is found that one-neutron stripping to the unbound nucleus He-5 is the dominant fragmentation mechanism and that it leads to a spin alignment of He-5 in a plane perpendicular to the He-5 momentum vector. This is expected to be a common feature for all neutron halo nuclei.
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| 9. |
- Nilsson, Thomas, 1965, et al.
(författare)
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He-6 and neutron momentum distributions from He-8 in nuclear break-up reactions at 240 MeV/u
- 1996
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Ingår i: Nuclear Physics A. - 0375-9474. ; 598:3, s. 418-434
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Tidskriftsartikel (refereegranskat)abstract
- Neutron and He-6 momentum distributions from He-8 break-up reactions in a C target have been measured at 240 MeV/u. The two-neutron removal cross section was found to be sigma(-2n) = 0.27 +/- 0.03 b. The nature of the momentum distributions is interpreted in some simple reaction scenarios.
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| 10. |
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| 11. |
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| 12. |
- Aleksandrov, D., et al.
(författare)
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Halo excitations in fragmentation of He-6 at 240 MeV/u on carbon and lead targets
- 2000
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Ingår i: Nuclear Physics A. - 0375-9474. ; 669:1-2, s. 51-64
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of a 240 MeV/u beam of He-6, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus He-6. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the He-6 inelastic scattering on carbon and lead targets were deduced from the measured moments of the two neutrons and the a-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in He-6 nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulornb post-acceleration in direct Coulomb breakup in a lead target.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Zinser, M., et al.
(författare)
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Invariant-mass spectroscopy of Li-10 and Li-11
- 1997
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Ingår i: Nuclear Physics A. - 0375-9474. ; 619:1-2, s. 151-176
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Tidskriftsartikel (refereegranskat)abstract
- Break-up of secondary Li-11 ion beams (280 MeV/nucleon) on C and Pb targets into Li-9 and neutrons is studied experimentally. Cross sections and neutron multiplicity distributions are obtained, characterizing different reaction mechanisms. Invariant-mass spectroscopy for Li-11 and Li-10 is performed. The E1 strength distribution, deduced from electromagnetic excitation of Li-11 up to an excitation energy of 4 MeV comprises similar to 8% of the Thomas-Reiche-Kuhn energy-weighted sumrule strength. Two low-lying resonance-like structures are observed for Li-10 at decay energies of 0.21(5) and 0.62(10) MeV, the former one carrying 26(10)% of the strength and likely to be associated with an s-wave neutron decay. A strong di-neutron correlation in Li-11 can be discarded. Calculations in a quasi-particle RPA approach are compared with the experimental results for Li-10 and Li-11. (C) 1997 Elsevier Science B.V.
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| 17. |
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| 18. |
- Da Silva Filho, M. I., et al.
(författare)
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Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts : Comparison with myeloma
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:8, s. 1735-1742
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used. For AL amyloidosis, single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at P<10 -5 with homogeneity of results from the 3 sample sets; some of these were previously documented to influence MM risk, including the SNP at the IRF4 binding site. In AL amyloidosis, rs9344 at the splice site of cyclin D1, promoting translocation (11;14), reached the highest significance, P=7.80 × 10 -11; the SNP was only marginally significant in MM. SNP rs79419269 close to gene SMARCD3 involved in chromatin remodeling was also significant (P=5.2 × 10 -8). These data provide evidence for common genetic susceptibility to AL amyloidosis and MM. Cyclin D1 is a more prominent driver in AL amyloidosis than in MM, but the links to aggregation of light chains need to be demonstrated.
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| 19. |
- Humbert, F., et al.
(författare)
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Longitudinal and Transverse-Momentum Distributions of Li-9 Fragments from Break-up of Li-11
- 1995
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 347:3-4, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- Transverse and longitudinal momentum distributions of Li-9 fragments from Li-11 break-up reactions in C, Al and Pb targets have been measured at 280 MeV/u. The two-neutron removal cross-section was measured to be sigma(-2n), = 0.26 +/- 0.02 b for the carbon target, sigma(-2n) = 0.47 +/- 0.08 b for the aluminum target and sigma(-2n), = 1.9 +/- 0.4 b for the lead target. No significant difference is observed between the narrow widths (FWHM approximate to 47 MeV/c) of the transverse and longitudinal momentum distributions of the Li-9 fragments. The physical implications of this are discussed.
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| 20. |
- Markenroth, Karin, 1973, et al.
(författare)
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He-8-He-6: a comparative study of nuclear fragmentation reactions
- 2001
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Ingår i: Nuclear Physics A. - 0375-9474. ; 679:3-4, s. 462-480
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of 227 MeV/u He-8 in a carbon target has been studied in kinematically complete experiments. The data include the relative energy spectrum, angular distributions in the neutron knock-out channel (He-6 + n) as well as diffractive dissociation and inelastic scattering into the (He-6 + 2n) channel. The data are compared with corresponding results from the well-known halo nucleus He-6. In both cases it is found that neutron knock-out is the: dominating reaction channel. The relative energy spectrum (He-6 + n) shows a structure, which is interpreted as being due to the I-pi = 3/2(-) resonance in the He-7 ground state with about equal contribution from its I-pi = 1/2(-) spin-orbit partner. The He-7 resonance shows a spin alignment similar to that observed in He-5, but with a smaller anisotropy indicating that the structure of the He-8 ground state is more complicated than that of He-6. The data in the (He-6 + 2n) channel were used to identify resonances in the excitation energy spectrum of He-8. If the spectrum is interpreted as two overlapping resonances, the spin-parity assignment for these is found to be 2(+) and 1(-), respectively.
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| 21. |
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| 22. |
- Nilsson, Thomas, 1965, et al.
(författare)
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Neutron Momentum Distributions from Core Break-up Reactions of Halo Nuclei
- 1995
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Ingår i: Europhysics Letters. - 0295-5075 .- 1286-4854. ; 30:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Neutron angular distributions from violent break-up reactions of Li-11 and Be-11 have been measured at 28 MeV/u and 280 MeV/u and at 41 MeV/u and 460 MeV/u, respectively. The derived neutron momentum distributions show a narrow component in transverse momentum that is within uncertainties independent of beam energy and target charge. This component is suggested to be simply related to the momentum distribution of the loosely bound halo neutron(s) in the projectiles.
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| 23. |
- Suliman, S., et al.
(författare)
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Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
- 2016
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 95, s. 11-21
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOKLuc) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOKLuc previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOKLuc + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOKLuc both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOKLuc + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOKLuc, while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
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| 24. |
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| 25. |
- Barthel, Roland, 1967, et al.
(författare)
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Linking the physical and the socio-economic compartments of an integrated water and land use management model on a river basin scale using an object-oriented water supply model
- 2005
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Ingår i: Physics and Chemistry of the Earth. - : Elsevier BV. - 1474-7065. ; 30:6-7, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- Within the framework of the research project 'GLOWA-Danube', a model of the water supply sector has been developed. GLOWA-Danube investigates long-term changes in the water cycle of the Upper Danube river basin in light of global change. For this purpose, the decision support system DANUBIA, comprising 15 fully coupled models, has been developed. Within DANUBIA the water supply model ('WaterSupply') forms the link between various physical models determining water quality and availability and several socio-economic models determining water consumption and demand. Having a central focus on public drinking water supply, its purpose is to correctly simulate the present day system of water extraction and distribution and the related costs, but also to allow meaningful response to possible future changes of boundary conditions, first and foremost changes in water demand or water availability and quality. Response mechanisms are also envisioned for changes in political and economic boundary conditions, and advances in technology. The model will be used locate critical regions which could experience water stress in the future, but does not aim to find the appropriate solutions or to predict the optimal organisation of water supply in the Danube Basin under such changing conditions. In the object-oriented model structure, both water supply companies (WSC) and communities are represented by main classes. Both classes have a limited view and knowledge of their environment. A community knows where and how much water is consumed and from which WSC it is served. A WSC possesses information regarding extraction sites and water rights, raw water quality and potential collaborating WSC. The WSC can perform actions that are different from 'business as usual'. These deviations from their usual behaviour can be interpreted by decision makers but should not be regarded as a replacement for the decision-making process itself. The model is conceptualised using object-oriented concepts of the Unified Modelling Language (UML) and is implemented in JAVA. This short overview is meant to answer key questions such as why and how WaterSupply was implemented, what is unique and new about the model and what are the general lessons learned and the added value with regard to integrated modelling on a river basin scale. It is obvious that in the attempt to answer these questions it is not possible to satisfy experts from all the relevant related fields, which include computer sciences, economy, behavioural science and not least water supply engineering and hydrology. (c) 2005 Elsevier Ltd. All rights reserved.
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| 26. |
- Baumann, T., et al.
(författare)
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Longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal from C-17,C-19
- 1998
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 439:3-4, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- The fragment separator FRS at GSI was used as an energy-loss spectrometer to measure the longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal reactions in C-17,C-19 impinging on a carbon target at about 910 MeV/u. The distributions in the projectile frames are characterized by a FWHM of 141 +/- 6 MeV/c for C-16 and 69 +/- 3 MeV/c for C-18. Th, results are compared with experimental data obtained at lower energies and discussed within existing theoretical models. (C) 1998 Elsevier Science B.V. AU rights reserved.
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| 27. |
- de Muynck, Ldan, et al.
(författare)
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Consensus Statement on the Use of Near-Infrared Fluorescence Imaging during Pancreatic Cancer Surgery Based on a Delphi Study: Surgeons' Perspectives on Current Use and Future Recommendations
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Despite the potential of fluorescence imaging during pancreatic cancer surgery, more research is needed to facilitate the approval of tumor-targeted probes, standardize imaging techniques, and most importantly, gain trust from surgeons. Despite advancements in the development of novel probes, preclinical research settings do not always accurately represent the surgical setting. This first-of-its-kind Delphi consensus survey highlights current experiences and attitudes towards fluorescence imaging during pancreatic cancer surgery, specifically from surgeon's perspectives. The results from this consensus survey highlight potential new directions for future research, which could facilitate the standardized use of fluorescence imaging during pancreatic surgery. Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons' perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with >= 70% agreement considered consensus and >= 80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS's benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS's use during PDAC surgery.
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| 28. |
- Endres, Dominique, et al.
(författare)
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Immunological causes of obsessive-compulsive disorder : is it time for the concept of an "autoimmune OCD" subtype?
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of "autoimmune OCD" is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for "autoimmune OCD" could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.
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| 29. |
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| 30. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 31. |
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| 32. |
- Arezzo, Alberto, et al.
(författare)
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EAES Recommendations for Recovery Plan in Minimally Invasive Surgery Amid COVID-19 Pandemic
- 2021
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Ingår i: Surgical Endoscopy. - : SPRINGER. - 0930-2794 .- 1432-2218. ; 35, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Background COVID-19 pandemic presented an unexpected challenge for the surgical community in general and Minimally Invasive Surgery (MIS) specialists in particular. This document aims to summarize recent evidence and experts opinion and formulate recommendations to guide the surgical community on how to best organize the recovery plan for surgical activity across different sub-specialities after the COVID-19 pandemic. Methods Recommendations were developed through a Delphi process for establishment of expert consensus. Domain topics were formulated and subsequently subdivided into questions pertinent to different surgical specialities following the COVID-19 crisis. Sixty-five experts from 24 countries, representing the entire EAES board, were invited. Fifty clinicians and six engineers accepted the invitation and drafted statements based on specific key questions. Anonymous voting on the statements was performed until consensus was achieved, defined by at least 70% agreement. Results A total of 92 consensus statements were formulated with regard to safe resumption of surgery across eight domains, addressing general surgery, upper GI, lower GI, bariatrics, endocrine, HPB, abdominal wall and technology/research. The statements addressed elective and emergency services across all subspecialties with specific attention to the role of MIS during the recovery plan. Eighty-four of the statements were approved during the first round of Delphi voting (91.3%) and another 8 during the following round after substantial modification, resulting in a 100% consensus. Conclusion The recommendations formulated by the EAES board establish a framework for resumption of surgery following COVID-19 pandemic with particular focus on the role of MIS across surgical specialities. The statements have the potential for wide application in the clinical setting, education activities and research work across different healthcare systems.
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| 33. |
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| 34. |
- Auffray, Charles, et al.
(författare)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
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Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 35. |
- Baalousha, M., et al.
(författare)
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Modeling nanomaterial fate and uptake in the environment: current knowledge and future trends
- 2016
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Ingår i: Environmental Science-Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161. ; 3:2, s. 323-345
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Tidskriftsartikel (refereegranskat)abstract
- Modeling the environmental fate of nanomaterials (NMs) and their uptake by cells and organisms in the environment is essential to underpin experimental research, develop overarching theories, improve our fundamental understanding of NM exposure and hazard, and thus enable risk assessment of NMs. Here, we critically review the state-of-the-art of the available models that can be applied/adapted to quantify/predict NM fate and uptake in aquatic and terrestrial systems and make recommendations regarding future directions for model development. Fate models have evolved from substance flow analysis models that lack nano-specific processes to more advanced mechanistic models that (at least partially) take nano-specific (typically non-equilibrium, dynamic) processes into account, with a focus on key fate processes such as agglomeration, sedimentation and dissolution. Similarly, NM uptake by organisms is driven by dynamic processes rather than by equilibrium partitioning. Hence, biokinetic models are more suited to model NM uptake, compared with the simple bio-accumulation factors used for organic compounds. Additionally, biokinetic models take speciation processes (e.g. particulate versus ionic uptake) into account, although identifying essential environment-specific processes to include in models remains a challenge. The models developed so far require parameterization, calibration and validation with available data, e.g. field data (if available), or experimental data (e.g. aquatic and terrestrial mesocosms), rather than extension to more complex and sophisticated models that include all possible transformation processes. Collaborative efforts between experimentalists and modelers to generate appropriate ground-truth data would advance the field most rapidly.
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| 36. |
- Barthel, Roland, 1967, et al.
(författare)
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An integrated modelling framework for simulating regional-scale actor responses to global change in the water domain
- 2008
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152. ; 23:9, s. 1095-1121
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Tidskriftsartikel (refereegranskat)abstract
- Within coupled hydrological simulation systems, taking socio-economic processes into account is still a challenging task. In particular, systems that aim at evaluating impacts of climatic change on large spatial and temporal scales cannot be based on the assumption that infrastructure, economy, demography and other human factors remain constant while physical boundary conditions change. Therefore, any meaningful simulation of possible future scenarios needs to enable socio-economic systems to react and to adapt to climatic changes. To achieve this it is necessary to simulate decision-making processes of the relevant actors in a way which is adequate for the scale, the catchment specific management problems to be investigated and finally the data availability. This contribution presents the DEEPACTOR approach for representing such human decision processes, which makes use of a multi-actor simulation framework and has similarities to agent-based approaches. This DEEPACTOR approach is embedded in DANUBIA, a coupled simulation system comprising 16 individual models to simulate Global Change impacts on the entire water cycle of the Upper Danube Catchment (Germany, 77,000 km(2)). The applicability of DANUBIA and in particular the DEEPACTOR approach for treating the socio-economic part of the water cycle in a process-based way is demonstrated by means of concrete simulation models of the water supply sector and of the domestic water users. Results from scenario simulations are used to demonstrate the capabilities and limitations of the approach. (c) 2008 Elsevier Ltd. All rights reserved.
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| 37. |
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| 38. |
- Barthel, Roland, 1967, et al.
(författare)
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Using the multiactor-approach in GLOWA-danube to simulate decisions for the water supply sector under conditions of global climate change
- 2010
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Ingår i: Water Resources Management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 24:2, s. 239-275
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Tidskriftsartikel (refereegranskat)abstract
- Glowa-Danube (www.glowa-danube.de) is an interdisciplinary project that aims to develop integrated strategies and tools for water and land use management in the upper Danube catchment (Germany, Austria ~77,000 km2). The project is one of five within the Glowa research program (www.glowa.org) dealing with Global Change effects on the water cycle in six meso-scale catchments (up to 100,000 km2) in Central Europe, West Africa and the Middle East. In the Glowa-Danube project, 16 natural science and socio-economic simulation models are integrated in the coupled simulation system Danubia. This article describes the underlying concept and implementation of WaterSupply, a multiactor-based model of the water supply sector with a focus on water resource utilization and distribution of individual water supply companies. Within Danubia, WaterSupply represents the link between water supply and demand, where the former is simulated by a groundwater and a surface water model and the latter by water consumption models of four different sectors (domestic, industrial, agricultural and tourism). WaterSupply interprets the quantitative state of water resources for defined spatial and temporal units according to sustainability requirements and assesses the state of resources in relation to present water supply schemes and the dynamics of user demand. WaterSupply then seeks both to optimize the resource use of supply companies and to identify critical regions for which further adaptation of the water supply scheme will become necessary under changing climatic conditions. In this article, a brief description of the Glowa-Danube project and the integrated simulation system Danubia is followed by a short presentation of the DeepActor framework, which provides a common conceptual and technical basis for the socio-economic simulation models of Glowa-Danube. The main body of the article is devoted to the concept, the implementation and simulation results of WaterSupply. Results from different scenario calculations demonstrate the capabilities and the potential fields of application of the model. © Springer Science+Business Media B.V. 2009.
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| 39. |
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| 40. |
- Chulkov, L. V., et al.
(författare)
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Three-body correlations in electromagnetic dissociation of Borromean nuclei: The He-6 case
- 2005
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 759:1-2, s. 23-42
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of He-6 on a lead target has been studied at 240 MeV/u. The four-momenta of the two neutrons in coincidence with alpha-particles have been measured and used to reconstruct the three-body energy and angular correlations in the final state. For the first time, three-body correlations were included in the analysis of the He-6 dissociation data, and compared with calculations assuming a dipole mode for the electromagnetic dissociation. In addition, the experimental data have been analyzed using a series expansion of the final transition amplitude into hyperspherical functions, showing the importance of both nn and alpha n final-state interactions. It is shown that the dissociation process is governed by a transition of one neutron from the p-shell in the 6He ground state to the s-shell in the continuum further indicating that the role of the transition through an intermediate He-5(3/2(-)) state is more important than expected. (c) 2005 Elsevier B.V. All rights reserved.
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| 41. |
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| 42. |
- Endres, Dominique, et al.
(författare)
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Spectrum of Novel Anti-Central Nervous System Autoantibodies in the Cerebrospinal Fluid of 119 Patients With Schizophreniform and Affective Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:4, s. 261-274
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed.METHODS: Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (n = 30), tissue-based testing was extended to a routine procedure (n = 89).RESULTS: Based on the findings from all 119 patients, anti-CNS immunoglobulin G autoantibodies against brain tissue were detected in 18% (n = 22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p =.026) and white matter changes (p =.020) more frequently than those who tested negative for autoantibodies.CONCLUSIONS: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.
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| 43. |
- Johnson, D C, et al.
(författare)
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Genetic factors influencing the risk of multiple myeloma bone disease.
- 2016
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 30, s. 883-888
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Tidskriftsartikel (refereegranskat)abstract
- A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totalling 3774) which had been radiologically surveyed for MBD. Each patient had been genotyped for ~600 000 SNPs with genotypes for six million common variants imputed using 1000Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio [OR]=1.38, P=4.09 × 10(-9)) and a promising association at 19q13.43 (rs74676832, OR=1.97, P=9.33 × 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.Leukemia accepted article preview online, 16 December 2015. doi:10.1038/leu.2015.342.
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| 44. |
- Johnson, David C, et al.
(författare)
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Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22-1.48, P=4.69 × 10(-9)). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors.
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| 45. |
- Labberton, L, et al.
(författare)
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Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12616-
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Tidskriftsartikel (refereegranskat)abstract
- Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.
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| 46. |
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| 47. |
- Larsson, M, et al.
(författare)
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When Life-Saving Is Life-Threatening
- 2014
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Ingår i: SCIENCE TRANSLATIONAL MEDICINE. - 1946-6234. ; 6:222
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 48. |
- Maricic, T, et al.
(författare)
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A direct RT-qPCR approach to test large numbers of individuals for SARS-CoV-2
- 2020
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12, s. e0244824-
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 causes substantial morbidity and mortality in elderly and immunocompromised individuals, particularly in retirement homes, where transmission from asymptomatic staff and visitors may introduce the infection. Here we present a cheap and fast screening method based on direct RT-qPCR to detect SARS-CoV-2 in single or pooled gargle lavages (“mouthwashes”). This method detects individuals with large viral loads (Ct≤29) and we use it to test all staff at a nursing home daily over a period of three weeks in order to reduce the risk that the infection penetrates the facility. This or similar approaches can be implemented to protect hospitals, nursing homes and other institutions in this and future viral epidemics.
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| 49. |
- Muche, M., et al.
(författare)
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Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients
- 2019
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 39:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Background Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). Methods HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). Results Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. Conclusions We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.
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| 50. |
- Nickel, Katrin F., et al.
(författare)
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The polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 126:11, s. 1379-1389
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies.
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