| 1. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 2. |
- Al Nimer, Faiez, et al.
(författare)
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Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination
- 2016
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Ingår i: Neurology. - 2332-7812. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.
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| 3. |
- Christensen, Jeppe Brage, et al.
(författare)
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A general algorithm for calculation of recombination losses in ionization chambers exposed to ion beams
- 2016
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405. ; 43:10
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dosimetry with ionization chambers in clinical ion beams for radiation therapy requires correction for recombination effects. However, common radiation protocols discriminate between initial and general recombination and provide no universal correction method for the presence of both recombination types in ion beams of charged particles heavier than protons. The advent of multiple field optimization in ion beams, allowing for complex patterns of dose delivery in both temporal and spatial domains, results in new challenges for recombination correction where the resulting recombination depends on the plan delivered. Here, the authors present the open source code IonTracks version 1.0, where the combined initial and general recombination effects in principle can be predicted for any ion beam with arbitrary particle-energy spectrum and temporal structure. Methods: IonTracks uses track structure theory to distribute the charge carriers in ion tracks. The charge carrier movements are governed by a pair of coupled differential equations, based on fundamental physical properties as charge carrier drift, diffusion, and recombination, which are solved numerically while the initial and general charge carrier recombination is computed. A space charge screening of the electric field is taken into account and the algorithm furthermore allows an inclusion of a free-electron component. Results: The algorithm is numerically stable and in accordance with experimentally validated theories for initial recombination in heavy ion tracks and general recombination in a proton beam. Conclusions: Given IonTracks' ability to handle arbitrary inputs, IonTracks can in principle be applied to any complex particle field in the spatial and temporal domain. IonTracks is validated against the Jaffe's and Boag's theory of recombination in pulsed beams of multiple ion species. IonTracks is able to calculate the correction factor for initial and general recombination losses in parallel-plate ionization chambers. Even if only few experimental data on recombination effects in ionization chambers are available today, the universal concept of IonTracks is not limited to the ions investigated here. Future experimental investigations of recombination in pulsed and possibly also continuous ion beams may be conducted with IonTracks, which ultimately may lead to a more precise prediction of recombination factors in complex radiation fields.
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| 4. |
- Christensen, Jeppe Brage, et al.
(författare)
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Ionization quenching in scintillators used for dosimetry of mixed particle fields
- 2019
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 64:9
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Tidskriftsartikel (refereegranskat)abstract
- Ionization quenching in ion beam dosimetry is often related to the fluence- or dose-averaged linear energy transfer (LET). Both quantities are however averaged over a wide LET range and a mixed field of primary and secondary ions. We propose a novel method to correct the quenched luminescence in scintillators exposed to ion beams. The method uses the energy spectrum of the primaries and accounts for the varying quenched luminescence in heavy, secondary ion tracks through amorphous track structure theory. The new method is assessed against more traditional approaches by correcting the quenched luminescence response from the BCF-12, BCF-60, and 81-0084 plastic scintillators exposed to a 100 MeV pristine proton beam in order to compare the effects of the averaged LET quantities and the secondary ions. Calculations and measurements show that primary protons constitute more than 92% of the energy deposition but account for more than 95% of the luminescence signal in the scintillators. The quenching corrected luminescence signal is in better agreement with the dose measurement when the secondary particles are taken into account. The Birks model provided the overall best quenching corrections, when the quenching corrected signal is adjusted for the number of free model parameters. The quenching parameter kB for the BCF-12 and BCF-60 scintillators is in agreement with literature values and was found to be kB = (10.6 +/- 0.1) x 10(-2) mu m keV(-1) for the 81-0084 scintillator. Finally, a fluence threshold for the 100 MeV proton beam was calculated to be of the order of 10(10) cm(-2), corresponding to 110 Gy, above which the quenching increases non-linearly and the Birks model no longer is applicable.
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| 5. |
- Christensen, Jeppe Brage, et al.
(författare)
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Quenching-free fluorescence signal from plastic-fibres in proton dosimetry : understanding the influence of Cerenkov radiation
- 2018
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:6
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Tidskriftsartikel (refereegranskat)abstract
- The origin of photons emitted in optical fibres under proton irradiation has been attributed to either entirely Cerenkov radiation or light consisting of fluorescence with a substantial amount of Cerenkov radiation. The source of the light emission is assessed in order to understand why the signal from optical fibres irradiated with protons is reportedly quenching-free. The present study uses the directional emittance of Cerenkov photons in 12 MeV and 20 MeV electron beams to validate a Monte Carlo model for simulating the emittance and transmission of Cerenkov radiation in optical fibres. We show that fewer than 0.01 Cerenkov photons are emitted and guided per 225 MeV proton penetrating the optical fibre, and that the Cerenkov signal in the optical fibre is completely negligible at the Bragg peak. Furthermore, on taking the emittance and guidance of both fluorescence and Cerenkov photons into account, it becomes evident that the reported quenching-free signal in PMMA-based optical fibres during proton irradiation is due to fluorescence.
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| 6. |
- Christensen, Jeppe
(författare)
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Layers of order - the past, present and future of superspace crystallography
- 2010
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Ingår i: Crystallography Reviews. - : Informa UK Limited. - 0889-311X .- 1476-3508. ; 16:2, s. 105-114
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Forskningsöversikt (refereegranskat)abstract
- The importance of having correct structural descriptions is becoming ever clearer, not only in drug discovery research, but also in the development of new advanced materials. Here the key to optimizing properties lies in understanding the structure-property relationships. Without a correct description theoretical calculations will inevitably fail to describe and explain any experimental observations. With increasing complexity of developed materials, modulated structures are likely to make up an increasing proportion of the structures to be investigated in the future. To take up this challenge, a development is needed in three areas of crystallography: The way we teach and what we teach our students; how we think about, and perform our crystallographic investigations; what tools are available, and how we use them. These areas are strongly coupled and any development in one is dependent on progress in the other two.
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| 7. |
- Christensen, Jeppe, 1975-
(författare)
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Non-Standard Crystallography : Examples in 3- and 3+1 Dimensional Space
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Crystallography today is by many seen as merely a tool for determining the structure of a material on the atomic level. It is expected that whatever comes out of the tool is the indisputable truth, a fact. This thesis is based on five publications illustrating that this is very far from the real world of materials research. The experiences drawn from the structural work in the papers are put together to illustrate when to be alert, and how to proceed with a structural investigation using non-standard crystallography. The focus is on interpreting the signs of additional order being present in a structure. The signs may be weak, such as extreme thermal vibration, or unit cell deformation. Or the signs can be strong, with superstructure reflections indicating the presence of either commensurate or incommensurate superstructures.
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| 8. |
- Christensen, Jeppe, et al.
(författare)
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Vacancy Ordering Effects in AlB2-type ErGe2-x(0.4 < x < or = 0.5)
- 2008
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Ingår i: Acta Crystallographica Section B. - 0108-7681 .- 1600-5740. ; 64:3, s. 272-280
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Tidskriftsartikel (refereegranskat)abstract
- In the Er-Ge system, the compostion range ErGe2 to Er2Ge3 has been investigated. Eight samples were produced by arc melting of the elements, and analyzed using X-ray powder diffraction. Nine crystal structures were found to be present in the samples. The structures are described as a homologous series and presented within the superspace formalism using the superspace group X2/m(0)0s, X representing the centring vector (½, ½, 0, ½). In this description the modulation vector q = (a* + c*) is shown to be a direct measure of the Ge content as ErGe2 - ( falls in the range to ½). The large composition range is achieved by extended vacancy ordering in the planar 63 net of Ge with subsequent relaxation.
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| 9. |
- Farnocchia, Davide, et al.
(författare)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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| 10. |
- Feuerbacher, Michael, et al.
(författare)
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The Samson phase, β-Mg2Al3, revisited
- 2007
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Ingår i: Zeitschrift fur Kristallographie. - : Walter de Gruyter GmbH. - 0044-2968. ; 222:6, s. 259-288
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Forskningsöversikt (refereegranskat)abstract
- The Al-Mg phase diagram has been reinvestigated in the vicinity of the stability range of the Samson phase, β-Mg2Al3 (cF1168). For the composition Mg38.5Al61.5, this cubic phase, space group Fd3̄m (no 227), a = 28.242(1) Å, V = 22526(2) Å3, undergoes at 214°C a first-order phase transition to rhombohedral β′-Mg2Al3, (hR293), a = 19.968(1) Å, c = 48.9114(8) Å, V = 16889(2) Å3, (i.e. 22519 Å3 for the equivalent cubic unit cell) space group R3m (no 160), a subgroup of index four of Fd3̄m. The structure of the β-phase has been redetermined at ambient temperature as well as in situ at 400°C. It essentially agrees with Samson's model, even in most of the many partially occupied and split positions. The structure of β′-Mg 2Al3 is closely related to that of the β-phase. Its atomic sites can be derived from those of the β-phase by group-theoretical considerations. The main difference between the two structures is that all atomic sites are fully occupied in case of the β′-phase. The reciprocal space, Bragg as well as diffuse scattering, has been explored as function of temperature and the β- to β′-phase transition was studied in detail. The microstructures of both phases have been analyzed by electron microscopy and X-ray topography showing them highly defective. Finally, the thermal expansion coefficients and elastic parameters have been determined. Their values are somewhere in between those of Al and Mg.
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