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- Rise, H. H., et al.
(författare)
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Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study
- 2022
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Ingår i: Neuroimage-Clinical. - : Elsevier BV. - 2213-1582. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. Methods: MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. Results: rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 x 10(-5)), and longitudinal changes in NfL (t =-2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). Discussion: In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.
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- Terazono, Y., et al.
(författare)
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Photonic control of photoinduced electron transfer via switching of redox potentials in a photochromic moiety
- 2004
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Ingår i: Journal of Physical Chemistry B. ; 108:6, s. 1812-1814
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Tidskriftsartikel (refereegranskat)abstract
- A porphyrin (P) has been covalently linked to a photochromic dihydroindolizine moiety (DHI) to form a P-DHI dyad. When the dihydroindolizine is in its closed, spirocyclic form (DHIc), the photophysics of the attached porphyrin are unaffected. Irradiation with UV light opens the photochromic moiety to the betaine form (DHIo), which has a significantly higher reduction potential than DHIc. Light absorption by the porphyrin moiety of P-DHIo is followed by rapid (50 ps) photoinduced electron transfer to yield the P.+-DHIo(.-) charge-seperated state. This state recombines in 2.9 ps to give the ground state. Irradiation of P-DHIo with light at wavelengths > 590 nm induces photoisomerization back to P-DHIc. Thermal closing can also be achieved. Thus, light is used to switch photoinduced electron transfer on or off. These principles may be useful in the design of molecular optoelectronic devices.
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- Barkholt, L., et al.
(författare)
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Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe
- 2006
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 17:7, s. 1134-1140
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Tidskriftsartikel (refereegranskat)abstract
- Background: An allogeneic antitumour effect has been reported for various cancers. We evaluated the experience of allogeneic haematopoietic stem cell transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21 European centres. Patients and methods: Reduced intensity conditioning and peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15 (range 3-41) months. Results: All but three patients engrafted. The cumulative incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n = 4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant, were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR 4.12, P < 0.001), DLI (HR 3.39, P < 0.001), < 3 metastatic sites (HR 2.61, P = 0.002) and a Karnofsky score > 70 (HR 2.33, P = 0.03). Patients (n = 17) with chronic GVHD and given DLI had a 2-year survival of 70%. Conclusion: Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score > 70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.
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- Brune-Ingebretsen, S., et al.
(författare)
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Immune cell subpopulations and serum neurofilament light chain are associated with increased risk of disease worsening in multiple sclerosis
- 2023
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Ingår i: Journal of Neuroimmunology. - 0165-5728. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Changes is lymphocyte subpopulations in peripheral blood have been proposed as biomarkers for evaluation of disease activity in multiple sclerosis (MS). Serum neurofilament light chain (sNfL) is a biomarker reflecting neuro-axonal injury in MS that could be used to monitor disease activity, response to drugs and to prognosticate disease course. Here we show a moderate correlation between sNfL and lymphocyte cell subpopulations, and our data furthermore suggest that sNfL and specific immune cell subpopulations together could predict future disease worsening in MS.
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- Brune, S., et al.
(författare)
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Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis
- 2022
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 28:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (> 8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5-5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.
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- Einarsdottir, Sigrun, et al.
(författare)
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Humoral immunity to tetanus, diphtheria and polio in adults after treatment for hematological malignancies
- 2020
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 38:5, s. 1084-1088
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Tidskriftsartikel (refereegranskat)abstract
- Introduction After chemotherapy, children with acute lymphocytic leukemia lose immunity and need revaccination against tetanus and diphtheria. However, little is known about immunity in adult patients after treatment for hematological malignancies. In this study, we assessed serology levels against polio, diphtheria and tetanus in adult patients after conventional treatment for leukemia and lymphoma. Patients One hundred and four patients, age 61 (19–86) years, were included at a median of 18 (4–77) months after chemotherapy for acute leukemia (n = 24) or lymphoma (n = 80). Pre-treatment sera were available in 73 cases for a pre-versus post treatment comparison. Healthy, age- and sex matched controls were available for 47 pts. Methods Tetanus antibodies were quantified using ELISA, and antibody levels ≥0.01 IU/mL were considered protective. Diphtheria antibodies were analyzed using neutralization test (n = 60) or by ELISA (n = 44). In both tests values ≥0.01 IU/mL were considered protective. Antibodies against poliovirus serotype 1 and 3 were assessed by a neutralizing test. A microneutralization titer of ≥2 was considered protective. Results Tetanus: There were significantly more non-immune patients after treatment (24%), compared to before (12%), p = 0.02. Post-treatment antibody levels were significantly lower than pre-treatment levels (p = 0.02). Diphtheria: There was a trend, p = 0.06, towards more non-immune patients after treatment (21%) compared to before (27%). Antibody levels post treatment were lower than pre treatment levels (p = 0.03) and lower than controls (p = 0.01). Polio: There was no significant difference in the number of non-immune patients before vs after chemotherapy for either PV1 or PV3. Protective immunity against serotype 1 and 3 was preserved in 90 and 97%, respectively. Conclusions After standard chemotherapy for leukemia and lymphoma a significant proportion of patients had impaired humoral immunity to diphtheria and tetanus. However, polio immunity was well preserved.
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- Hannestad, Jonas, 1981, et al.
(författare)
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Kinetics of Diffusion-Mediated DNA Hybridization in Lipid Monolayer Films Determined by Single-Molecule Fluorescence Spectroscopy
- 2013
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 7:1, s. 308-315
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Tidskriftsartikel (refereegranskat)abstract
- We use single-molecule fluorescence microscopy to monitor individual hybridization reactions between membrane-anchored DNA strands, occurring in nanofluidic lipid monolayer films deposited on Teflon AF substrates. The DNA molecules are labeled with different fluorescent dyes, which make it possible to simultaneously monitor the movements of two different molecular species, thus enabling tracking of both reactants and products. We employ lattice diffusion simulations to determine reaction probabilities upon interaction. The observed hybridization rate of the 40-mer DNA was more than 2-fold higher than that of the 20-mer DNA. Since the lateral diffusion coefficient of the two different constructs is nearly identical, the effective molecule radius determines the overall kinetics. This implies that when two DNA molecules approach each other, hydrogen bonding takes place distal from the place where the DNA is anchored to the surface. Strand closure then propagates bidirectionally through a zipper-like mechanism, eventually bringing the lipid anchors together. Comparison with hybridization rates for corresponding DNA sequences in solution reveals that hybridization rates are lower for the lipid-anchored strands and that the dependence on strand length is stronger.
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| 25. |
- Johnson, Calvin W., et al.
(författare)
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White paper: From bound states to the continuum
- 2020
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:12
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Forskningsöversikt (refereegranskat)abstract
- This white paper reports on the discussions of the 2018 Facility for Rare Isotope Beams Theory Alliance (FRIB-TA) topical program ‘From bound states to the continuum: Connecting bound state calculations with scattering and reaction theory’. One of the biggest and most important frontiers in nuclear theory today is to construct better and stronger bridges between bound state calculations and calculations in the continuum, especially scattering and reaction theory, as well as teasing out the influence of the continuum on states near threshold. This is particularly challenging as many-body structure calculations typically use a bound state basis, while reaction calculations more commonly utilize few-body continuum approaches. The many-body bound state and few-body continuum methods use different language and emphasize different properties. To build better foundations for these bridges, we present an overview of several bound state and continuum methods and, where possible, point to current and possible future connections.
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