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| 2. |
- Mitchell, Jonathan S., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 3. |
- Nilsson Ekdahl, Kristina, et al.
(author)
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Dangerous liaisons : complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
- 2016
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In: Immunological Reviews. - : Wiley. - 0105-2896 .- 1600-065X. ; 274:1, s. 245-269
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Research review (peer-reviewed)abstract
- Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.
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| 4. |
- Santillo, Alexander Frizell, et al.
(author)
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Grey and white matter clinico-anatomical correlates of disinhibition in neurodegenerative disease
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
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Journal article (peer-reviewed)abstract
- Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico- anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information- based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insularorbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the prefrontal syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.
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| 5. |
- Ahlgren, André, et al.
(author)
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Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data.
- 2016
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In: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 29:5, s. 640-649
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Journal article (peer-reviewed)abstract
- The aim of this study was to improve the accuracy and precision of perfusion fraction and blood velocity dispersion estimates in intravoxel incoherent motion (IVIM) imaging, using joint analysis of flow-compensated and non-flow-compensated motion-encoded MRI data. A double diffusion encoding sequence capable of switching between flow-compensated and non-flow-compensated encoding modes was implemented. In vivo brain data were collected in eight healthy volunteers and processed using the joint analysis. Simulations were used to compare the performance of the proposed analysis method with conventional IVIM analysis. With flow compensation, strong rephasing was observed for the in vivo data, approximately cancelling the IVIM effect. The joint analysis yielded physiologically reasonable perfusion fraction maps. Estimated perfusion fractions were 2.43 ± 0.81% in gray matter, 1.81 ± 0.90% in deep gray matter, and 1.64 ± 0.72% in white matter (mean ± SD, n = 8). Simulations showed improved accuracy and precision when using joint analysis of flow-compensated and non-flow-compensated data, compared with conventional IVIM analysis. Double diffusion encoding with flow compensation was feasible for in vivo imaging of the perfusion fraction in the brain. The strong rephasing implied that blood flowing through the cerebral microvascular system was closer to the ballistic limit than the diffusive limit. © 2016 The Authors NMR in Biomedicine published by John Wiley & Sons Ltd.
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| 6. |
- Beye, Martin, et al.
(author)
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Chemical Bond Activation Observed with an X-ray Laser
- 2016
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 7:18, s. 3647-3651
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Journal article (peer-reviewed)abstract
- The concept of bonding and antibonding orbitals is fundamental in chemistry. The population of those orbitals and the energetic difference between the two reflect the strength of the bonding interaction. Weakening the bond is expected to reduce this energetic splitting, but the transient character of bond-activation has so far prohibited direct experimental access. Here we apply time-resolved soft X-ray spectroscopy at a free electron laser to directly observe the decreased bonding antibonding splitting following bond-activation using an ultrashort optical laser pulse.
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| 7. |
- Bonnefoy, M., et al.
(author)
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First light of the VLT planet finder SPHERE IV. Physical and chemical properties of the planets around HR8799
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Journal article (peer-reviewed)abstract
- Context. The system of four planets discovered around the intermediate-mass star HR8799 offers a unique opportunity to test planet formation theories at large orbital radii and to probe the physics and chemistry at play in the atmospheres of self-luminous young (similar to 30 Myr) planets. We recently obtained new photometry of the four planets and low-resolution (R similar to 30) spectra of HR8799 d and e with the SPHERE instrument (Paper III).Aims. In this paper (Paper IV), we aim to use these spectra and available photometry to determine how they compare to known objects, what the planet physical properties are, and how their atmospheres work.Methods. We compare the available spectra, photometry, and spectral energy distribution (SED) of the planets to field dwarfs and young companions. In addition, we use the extinction from corundum, silicate (enstatite and forsterite), or iron grains likely to form in the atmosphere of the planets to try to better understand empirically the peculiarity of their spectrophotometric properties. To conclude, we use three sets of atmospheric models (BT-SETTL14, Cloud-AE60, Exo-REM) to determine which ingredients are critically needed in the models to represent the SED of the objects, and to constrain their atmospheric parameters (T-eff, log g, M/H).Results. We find that HR8799d and e properties are well reproduced by those of L6-L8 dusty dwarfs discovered in the field, among which some are candidate members of young nearby associations. No known object reproduces well the properties of planets b and c. Nevertheless, we find that the spectra and WISE photometry of peculiar and/or young early-T dwarfs reddened by submicron grains made of corundum, iron, enstatite, or forsterite successfully reproduce the SED of these planets. Our analysis confirms that only the Exo-REM models with thick clouds fit (within 2 sigma) the whole set of spectrophotometric datapoints available for HR8799 d and e for T-eff = 1200 K, log g in the range 3.0-4.5, and M/H = +0.5. The models still fail to reproduce the SED of HR8799c and b. The determination of the metallicity, log g, and cloud thickness are degenerate.Conclusions. Our empirical analysis and atmospheric modelling show that an enhanced content in dust and decreased CIA of H-2 is certainly responsible for the deviation of the properties of the planet with respect to field dwarfs. The analysis suggests in addition that HR8799c and b have later spectral types than the two other planets, and therefore could both have lower masses.
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| 8. |
- De Palma, Adriana, et al.
(author)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
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Journal article (peer-reviewed)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 9. |
- Dublon, Ian, et al.
(author)
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Scintillate : An open-source graphical viewer for time-series calcium imaging evaluation and pre-processing
- 2016
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In: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 273, s. 120-127
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Journal article (peer-reviewed)abstract
- Background Calcium imaging is based on the detection of minute signal changes in an image time-series encompassing pre- and post-stimuli. Depending on the function of the elicited response, change may be pronounced, as in the case of a genetically encoded calcium-reporter protein, or subtle, as is the case in a bath-applied dye system. Large datasets are thus often acquired and appraised only during post-processing where specific Regions of Interest (ROIs) are examined. New method The scintillate software provides a platform allowing for near instantaneous viewing of time-sequenced tiffs within a discrete GUI environment. Whole sequences may be evaluated. In its simplest form scintillate provides change in florescence (ΔF) across the entire tiff image matrix. Evaluating image intensity level differences across the whole image allows the user to rapidly establish the value of the preparation, without a priori ROI-selection. Additionally, an implementation of Independent Component Analysis (ICA) provides additional rapid insights into areas of signal change. Results We imaged transgenic flies expressing Calcium-sensitive reporter proteins within projection neurons and moth mushroom bodies stained with a Ca2+ sensitive bath-applied dye. Instantaneous pre-stimulation background subtraction allowed us to appraise strong genetically encoded neuronal Ca2+ responses in flies and weaker, less apparent, responses within moth mushroom bodies. Comparison with existing methods At the time of acquisition, whole matrix ΔF analysis alongside ICA is ordinarily not performed. We found it invaluable, minimising time spent with unresponsive samples, and assisting in optimisation of subsequent acquisitions. Conclusions We provide a multi-platform open-source system to evaluate time-series images.
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| 10. |
- Falk Delgado, Anna, et al.
(author)
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Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III : A Prospective Cohort Study
- 2016
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In: Radiology research and practice. - : Hindawi Limited. - 2090-1941 .- 2090-195X. ; 2016:1, s. 1-15
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Journal article (peer-reviewed)abstract
- Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.
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