| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Backis, A., et al.
(author)
-
Time- and energy-resolved effects in the boron-10 based multi-grid and helium-3 based thermal neutron detectors
- 2021
-
In: Measurement science and technology. - : IOP PUBLISHING LTD. - 0957-0233 .- 1361-6501. ; 32:3
-
Journal article (peer-reviewed)abstract
- The boron-10 based multi-grid detector is being developed as an alternative to helium-3 based neutron detectors. At the European Spallation Source, the detector will be used for time-of-flight neutron spectroscopy at cold to thermal neutron energies. The objective of this work is to investigate fine time- and energy-resolved effects of the Multi-Grid detector, down to a few mu eV, while comparing it to the performance of a typical helium-3 tube. Furthermore, it is to characterize differences between the detector technologies in terms of internal scattering, as well as the time reconstruction of similar to mu s short neutron pulses. The data were taken at the Helmholtz Zentrum Berlin, where the Multi-Grid detector and a helium-3 tube were installed at the ESS test beamline, V20. Using a Fermi-chopper, the neutron beam of the reactor was chopped into a few tens of mu s wide pulses before reaching the detector, located a few tens of cm downstream. The data of the measurements show an agreement between the derived and calculated neutron detection efficiency curve. The data also provide fine details on the effect of internal scattering, and how it can be reduced. For the first time, the chopper resolution was comparable to the timing resolution of the Multi-Grid detector. This allowed a detailed study of time- and energy resolved effects, as well as a comparison with a typical helium-3 tube.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Serra Filho, L. A., et al.
(author)
-
Double-GEM based thermal neutron detector prototype
- 2022
-
In: Journal of Instrumentation. - : IOP Publishing Ltd. - 1748-0221 .- 1748-0221. ; 17:9
-
Journal article (peer-reviewed)abstract
- The Helium-3 shortage and the growing interest in neutron science constitute a driving factor in developing new neutron detection technologies. In this work, we report the development of a double-GEM detector prototype that uses a (B4C)-B-10 layer as a neutron converter material. GEANT4 simulations were performed predicting an efficiency of (3.14 +/- 0.10)%, agreeing within 2.7 sigma with the experimental and analytic detection efficiencies obtained by the detector when tested in a 41.8 meV thermal neutron beam. The detector is position sensitive, equipped with a 256+256 strip readout connected to resistive chains, and achieves a spatial resolution better than 3 mm. The gain stability over time was also measured with a fluctuation of about 0.2% h(-1) of the signal amplitude. A simple data acquisition with only 5 electronic channels is sufficient to operate this detector.
|
|
| 8. |
- Wilking, N., et al.
(author)
-
Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
-
In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
-
Journal article (peer-reviewed)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
|
|
| 9. |
- Onatsu, J., et al.
(author)
-
Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events
- 2020
-
In: In Vivo. - : Anticancer Research USA Inc.. - 0258-851X .- 1791-7549. ; 34:5, s. 2577-2586
-
Journal article (peer-reviewed)abstract
- Background/Aim: We aimed to analyze the diagnostic value of total tau (T- tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. Patients and Methods: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8 +/- 50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. Results: T-tau was higher in patients with stroke (1.0 pg/ml (IQR=0.3-2 2)] than with TIA (05 pg/ml (IQR=0.2- 1 .0), p=0.02] . The levels of S100B were also increased in stroke [0.082 mu g/l (IQR=0.049-0.157)] patients compared to TIA patients (0.045 mu g/l (IQR=0.03 -0.073 ), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 mu g/l (IQR=9.30-16.14)] compared to those with TIA (10.96 mu g/l (IQR=7 .98-15.33), p=0.301 were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). Conclusion: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Birgersson, Sofia, 1976, et al.
(author)
-
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: An open label trial [version 2; peer review: 2 approved]
- 2020
-
In: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 4
-
Journal article (peer-reviewed)abstract
- Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008). © 2020 Birgersson S et al.
|
|
| 13. |
- Johansson, S, et al.
(author)
-
Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules
- 2005
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 201:7, s. 1145-1155
-
Journal article (peer-reviewed)abstract
- The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (Kb, Db, Dd, or Ld) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I–deficient cells in an NK cell–dependent way. Expression of Kb or Dd conveyed strong rejection of MHC class I–deficient cells, whereas the expression of Db or Ld resulted in weaker responses. The educating impact of weak ligands (Db and Ld) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (Kb and Dd) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I–Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.
|
|
| 14. |
- Juliusson, Gunnar, et al.
(author)
-
Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.
- 2006
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:1, s. 42-47
-
Journal article (peer-reviewed)abstract
- Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention ( RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region ( range 36-76%) and the two-year overall survival, with no censored observations (6-21%) ( v 2 for trend = 11.3, P < 0.001; r(2) = 0.86, P < 0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates ( P = 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Mustjoki, S., et al.
(author)
-
Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
-
Journal article (peer-reviewed)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
|
|
| 20. |
|
|
| 21. |
- Tong, M., et al.
(author)
-
An integrated framework for multi-scale multi-physics numerical modelling of interface evolution in welding
- 2012
-
In: IOP Conf. Ser. Mater. Sci. Eng..
-
Conference paper (peer-reviewed)abstract
- The project Modelling of Interface evolution in advanced Welding (MIntWeld) is a 4-year international research project funded by the European Commission under their FP7 programme. Its main target is to develop a numerical toolbox which can be used to predict the evolution of interfaces during welding. There are various interfaces involving multiple phenomena and different spatial scales, which can be simulated using corresponding numerical modelling methods respectively. The modelling methods include quantum dynamics, molecular dynamics, phase field, phase field crystal, computational fluid dynamics, phase transformation and heat transfer, thermodynamics, continuum mechanics and life and defects prediction. Although each modelling method is based on different physical theories and involves different scales, they are not isolated. Therefore, this project aims to design a common framework which couples each model with the upstream and/or downstream model at the relevant neighbouring length scales. The data exchange framework which underpins the coupling of the models is described, and typical examples addressing the solution to the challenges faced, such as those of data interpolation between one discretisation of the computational domain and another, are discussed. Initial successes from the model-linking efforts of the authors are also presented.
|
|
| 22. |
|
|
| 23. |
- Albrecht, Daniel S., et al.
(author)
-
Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation
- 2019
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 75, s. 72-83
-
Journal article (peer-reviewed)abstract
- Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Meier, H. E. M., et al.
(author)
-
modeling the combined impact of changing climate and changing nutrient loads on the baltic sea environment in an ensemble of transient simulations for 1961 2099
- 2012
-
In: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 39:9-10, s. 2421-2441
-
Journal article (peer-reviewed)abstract
- The combined future impacts of climate change and industrial and agricultural practices in the Baltic Sea catchment on the Baltic Sea ecosystem were assessed. For this purpose 16 transient simulations for 1961-2099 using a coupled physical-biogeochemical model of the Baltic Sea were performed. Four climate scenarios were combined with four nutrient load scenarios ranging from a pessimistic business-as-usual to a more optimistic case following the Baltic Sea Action Plan (BSAP). Annual and seasonal mean changes of climate parameters and ecological quality indicators describing the environmental status of the Baltic Sea like bottom oxygen, nutrient and phytoplankton concentrations and Secchi depths were studied. Assuming present-day nutrient concentrations in the rivers, nutrient loads from land increase during the twenty first century in all investigated scenario simulations due to increased volume flows caused by increased net precipitation in the Baltic catchment area. In addition, remineralization rates increase due to increased water temperatures causing enhanced nutrient flows from the sediments. Cause-and-effect studies suggest that both processes may play an important role for the biogeochemistry of eutrophicated seas in future climate partly counteracting nutrient load reduction efforts like the BSAP.
|
|
| 32. |
- Ramos Santesmases, David, et al.
(author)
-
Quasi-3-dimensional simulations and experimental validation of surface leakage currents in high operating temperature type-II superlattice infrared detectors
- 2022
-
In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 132:20, s. 204501-
-
Journal article (peer-reviewed)abstract
- The surface leakage in InAs/GaSb type-II superlattice (T2SL) is studied experimentally and theoretically for photodiodes with small sizes down to 10 x 10 mu m(2). The dependence of dark current density on mesa size is studied at 110 and 200 K, and surface leakage is shown to impact both generation-recombination (GR) and diffusion dark current mechanisms. A quasi-3-dimensional model to simulate the fabrication process using surface traps on the pixel's sidewall is presented and is used to accurately represent the dark current of large and small pixels with surface leakage in the different temperature regimes. The simulations confirmed that the surface leakage current has a GR and diffusion component at low and high temperature, respectively. Finally, the surface leakage current has been correlated with the change in minority carrier concentration at the surface due to the presence of donor traps.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Vindas, Marco A., et al.
(author)
-
Early life stress induces long-term changes in limbic areas of a teleost fish: the role of catecholamine systems in stress coping
- 2018
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- Early life stress (ELS) shapes the way individuals cope with future situations. Animals use cognitive flexibility to cope with their ever-changing environment and this is mainly processed in forebrain areas. We investigated the performance of juvenile gilthead seabream, previously subjected to an ELS regime. ELS fish showed overall higher brain catecholaminergic (CA) signalling and lower brain derived neurotrophic factor (bdnf) and higher cfos expression in region-specific areas. All fish showed a normal cortisol and serotonergic response to acute stress. Brain dopaminergic activity and the expression of the alpha(2A) adrenergic receptor were overall higher in the fish homologue to the lateral septum (Vv), suggesting that the Vv is important in CA system regulation. Interestingly, ELS prevented post-acute stress downregulation of the alpha(2A) receptor in the amygdala homologue (Dm3). There was a lack of post-stress response in the beta(2) adrenergic receptor expression and a downregulation in bdnf in the Dm3 of ELS fish, which together indicate an allostatic overload in their stress coping ability. ELS fish showed higher neuronal activity (cfos) post-acute stress in the hippocampus homologue (Dlv) and the Dm3. Our results show clear long-term effects on limbic systems of seabream that may compromise their future coping ability to environmental challenges.
|
|
