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| 3. |
- Mallet, E, et al.
(author)
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A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety
- 2004
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 22:11-12, s. 1343-1357
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Research review (peer-reviewed)abstract
- To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac((R)); Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac((R)) has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac((R)) also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac(TM) (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax(TM) II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac((R)) administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac((R)) at 3 and 5 months with a booster at 12 months of age. Hexavac((R)) demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac((R)) provided immunity against six important childhood diseases with a single injection at each visit. (C) 2003 Elsevier Ltd. All rights reserved.
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| 4. |
- Bentmann, H., et al.
(author)
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Strong Linear Dichroism in Spin-Polarized Photoemission from Spin-Orbit-Coupled Surface States
- 2017
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In: Physical Review Letters. - 0031-9007. ; 119:10
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Journal article (peer-reviewed)abstract
- A comprehensive understanding of spin-polarized photoemission is crucial for accessing the electronic structure of spin-orbit coupled materials. Yet, the impact of the final state in the photoemission process on the photoelectron spin has been difficult to assess in these systems. We present experiments for the spin-orbit split states in a Bi-Ag surface alloy showing that the alteration of the final state with energy may cause a complete reversal of the photoelectron spin polarization. We explain the effect on the basis of ab initio one-step photoemission theory and describe how it originates from linear dichroism in the angular distribution of photoelectrons. Our analysis shows that the modulated photoelectron spin polarization reflects the intrinsic spin density of the surface state being sampled differently depending on the final state, and it indicates linear dichroism as a natural probe of spin-orbit coupling at surfaces.
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| 5. |
- Dyrskjot, L., et al.
(author)
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Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
- 2012
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 107:8, s. 1392-1398
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
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| 6. |
- Horio, M., et al.
(author)
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Oxide Fermi liquid universality revealed by electron spectroscopy
- 2020
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 102:24
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Journal article (peer-reviewed)abstract
- We present a combined soft x-ray and high-resolution vacuum-ultraviolet angle-resolved photoemission spectroscopy study of the electron-overdoped cuprate Pr1.3-xLa0.7CexCuO4 (PLCCO). Demonstration of its highly two-dimensional band structure enabled precise determination of the in-plane self-energy dominated by electron-electron scattering. Through analysis of this self-energy and the Fermi liquid cut-off energy scale, we find-in contrast to hole-doped cuprates-a momentum isotropic and comparatively weak electron correlation in PLCCO. Yet, the self-energies extracted from multiple oxide systems combine to demonstrate a logarithmic divergent relation between the quasiparticle scattering rate and mass. This constitutes a spectroscopic version of the Kadowaki-Woods relation with an important merit-the demonstration of Fermi liquid quasiparticle lifetime and mass being set by a single energy scale.
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| 7. |
- Islam, Fhokrul, et al.
(author)
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Systematics of electronic and magnetic properties in the transition metal doped Sb2Te3 quantum anomalous Hall platform
- 2018
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In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 97:15
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Journal article (peer-reviewed)abstract
- The quantum anomalous Hall effect (QAHE) has recently been reported to emerge in magnetically doped topological insulators. Although its general phenomenology is well established, the microscopic origin is far from being properly understood and controlled. Here, we report on a detailed and systematic investigation of transition metal (TM) doped Sb2Te3. By combining density functional theory calculations with complementary experimental techniques, i.e., scanning tunneling microscopy, resonant photoemission, and x-raymagnetic circular dichroism, we provide a complete spectroscopic characterization of both electronic and magnetic properties. Our results reveal that the TM dopants not only affect the magnetic state of the host material, but also significantly alter the electronic structure by generating impurity-derived energy bands. Our findings demonstrate the existence of a delicate interplay between electronic and magnetic properties in TM doped topological insulators. In particular, we find that the fate of the topological surface states critically depends on the specific character of the TM impurity: while V-and Fe-doped Sb2Te3 display resonant impurity states in the vicinity of the Dirac point, Cr and Mn impurities leave the energy gap unaffected. The single-ion magnetic anisotropy energy and easy axis, which control the magnetic gap opening and its stability, are also found to be strongly TM impurity dependent and can vary from in plane to out of plane depending on the impurity and its distance from the surface. Overall, our results provide general guidelines for the realization of a robust QAHE in TM doped Sb2Te3 in the ferromagnetic state.
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| 8. |
- Meyer, F., et al.
(author)
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"Building Block Picture" of the Electronic Structure of Aqueous Cysteine Derived from Resonant Inelastic Soft X-ray Scattering
- 2014
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 118:46, s. 13142-13150
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Journal article (peer-reviewed)abstract
- The electronic structure of the amino acid l-cysteine in an aqueous environment was studied using resonant inelastic soft X-ray scattering (RIXS) in a 2D map representation and analyzed in the framework of a building block approach. The element selectivity of RIXS allows a local investigation of the electronic structure of the three functional groups of cysteine, namely, the carboxyl, amino, and thiol groups, by measuring at the O K, N K, and S L-2,L-3 edges, respectively. Variation of the pH value allows an investigation of molecules with protonated and deprotonated functional groups, which can then be compared with simple reference molecules that represent the isolated functional groups. We find that such building blocks can provide an excellent description of X-ray emission spectroscopy (XES) and RIXS spectra, but only if all nearest-neighbor atoms are included. This finding is analogous to the building block principle commonly used in X-ray absorption spectroscopy. The building blocks show a distinct spectral character (fingerprint) and allow a comprehensive interpretation of the cysteine spectra. This simple approach opens the path to investigate the electronic structure of more complex biological molecules in aqueous solutions using XES and RIXS.
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| 9. |
- Dyrskjot, Lars, et al.
(author)
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Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study
- 2017
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 461-469
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Journal article (peer-reviewed)abstract
- Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.
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| 10. |
- Fristrup, Niels, et al.
(author)
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Multicenter Validation of Cyclin D1, MCM7, TRIM29, and UBE2C as Prognostic Protein Markers in Non-Muscle Invasive Bladder Cancer
- 2013
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In: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 182:2, s. 339-349
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Journal article (peer-reviewed)abstract
- Transcripts from the four genes encoding cyclin D1, MCM7, TRIM29, and UBE2C have previously been included in gene expression signatures for outcome prediction in stage Ta/T1 urothelial carcinomas. We investigated the prognostic value of the protein expressions in Ta/T1 urothelial carcinomas patients. We used four different tissue microarrays (TMAs) with a total of 859 Ta/T1 urothelial carcinomas from Danish, Swedish, Spanish, and Taiwanese patient cohorts with long-term follow-up. Protein expression was measured by IHC, and antibody specificity was validated by Western blotting. We found the expression of cyclin D1, MCM7, TRIM29, and UBE2C to be significantly associated with progression to muscle invasive bladder cancer (log-rank test; P < 0.001) in the Danish training cohort (n = 283). Multivariate Cox regression analysis identified cyclin D1 (P = 0.003), TRIM29 (P = 0.001), and UBE2C (P < 0.001) as independent prognostic markers. The prognostic value of the four proteins was validated in a joint validation cohort from Sweden, Spain, and Taiwan (n = 576). Computer-assisted image analysis of the prognostic markers produced results comparable to those obtained by manual scoring. Finally, a four-protein maximum-likelihood classifier was trained on the Danish training cohort and applied to the validation cohort. The four protein markers may help optimize treatment of patients with Ta/T1 bladder cancer. Additional prospective studies are needed for further validation of their clinical relevance.
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| 11. |
- Iversen, M. B., et al.
(author)
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An innate antiviral pathway acting before interferons at epithelial surfaces
- 2016
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In: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:2, s. 150-158
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Journal article (peer-reviewed)abstract
- Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.
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| 12. |
- Karlsen, Reinert Huseby, et al.
(author)
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A post audit and inverse modeling in reactive transport : 50 years of artificial recharge in the Amsterdam Water Supply Dunes
- 2012
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In: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 454, s. 7-25
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Journal article (peer-reviewed)abstract
- This article describes the post audit and inverse modeling of a 1-D forward reactive transport model. The model simulates the changes in water quality following artificial recharge of pre-treated water from the river Rhine in the Amsterdam Water Supply Dunes using the PHREEQC-2 numerical code. One observation dataset is used for model calibration, and another dataset for validation of model predictions. The total simulation time of the model is 50 years, from 1957 10 2007, with recharge composition varying on a monthly basis and the post audit is performed 26 years after the former model simulation period. The post audit revealed that the original model could reasonably predict conservative transport and kinetic redox reactions (oxygen and nitrate reduction coupled to the oxidation of soil organic carbon), but showed discrepancies in the simulation of cation exchange. Conceptualizations of the former model were inadequate to accurately simulate water quality changes controlled by cation exchange, especially concerning the breakthrough of potassium and magnesium fronts. Changes in conceptualization and model design, including the addition of five flow paths, to a total of six, and the use of parameter estimation software (PEST), resulted in a better model to measurement fit and system representation. No unique parameter set could be found for the model, primarily due to high parameter correlations, and an assessment of the predictive error was made using a calibration constrained Monte-Carlo method, and evaluated against field observations. The predictive error was found to be low for Na+ and Ca2+, except for greater travel times, while the K+ and Mg2+ error was restricted to the exchange fronts at some of the flow paths. Optimized cation exchange coefficients were relatively high, especially for potassium, but still within the observed range in literature. The exchange coefficient for potassium agrees with strong fixation on illite, a main clay mineral in the area. Optimized CEC values were systematically lower than clay and organic matter contents indicated, possibly reflecting preferential flow of groundwater through the more permeable but less reactive aquifer parts. Whereas the artificial recharge initially acted as an intrusion of relatively saline water triggering Na+ for Ca2+ exchange, further increasing total hardness of the recharged water, the gradual long-term reduction in salinity of the river Rhine since the mid 1970s has shifted to an intrusion of fresher water causing Ca2+ for Na+ exchange. As a result, seasonal and longer term reversal of the initial cation exchange processes was observed adding to the general long-term reduction in total hardness of the recharged Rhine water.
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| 14. |
- Lekki, J., et al.
(author)
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On the follicular pathway of percutaneous uptake of nanoparticles: Ion microscopy and autoradiography studies
- 2007
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In: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 260:1, s. 174-177
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Journal article (peer-reviewed)abstract
- We report on the visualization of the penetration of sunscreen formulations containing TiO2 nanoparticles (about 20 nm primary particle size) into hair follicles of both human and porcine skin using the complementary methods of ion microscopy (PIXE, RBS, STIM) and autoradiography. Particles were found as deep as approx. 400 pin in the follicle, obviously introduced mechanically rather than by a diffusive process. No particles were observed in vital tissue nor in sebaceous glands. (c) 2007 Elsevier B.V. All rights reserved.
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