| 1. |
- Capala, J, et al.
(author)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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In: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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Journal article (peer-reviewed)abstract
- A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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- Brynjolfsson, Siggeir, et al.
(author)
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Long-lived plasma cells in mice and men
- 2018
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Journal article (peer-reviewed)abstract
- Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans. © 2007 - 2018 Frontiers Media S.A.
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| 5. |
- Campieri, M, et al.
(author)
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Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group
- 1997
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 41:2, s. 209-214
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Journal article (peer-reviewed)abstract
- Background—The use of corticosteroids in active Crohn’s disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.Aims—To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn’s disease affecting the ileum and/or the ascending colon.Patients and methods—One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn’s Disease Activity Index (CDAI) of 150 or less.Results—After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p=0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p=0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p=0.0023).Conclusions—Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn’s disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.
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- Fernández-Santoscoy, Maria, et al.
(author)
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A reduced population of CD103(+)CD11b(+) dendritic cells has a limited impact on oral Salmonella infection
- 2016
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In: Immunology Letters. - : Elsevier BV. - 0165-2478. ; 176, s. 72-80
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Journal article (peer-reviewed)abstract
- CD103(+)CD11b(+) dendritic cells (DC) are the major migratory DC subset in the small intestine lamina propria (siLP) and their survival is dependent on the transcription factor interferon regulatory factor 4 (IRF4). Mice with a DC-specific deletion of irf4 (CD11c-cre.Irf4 mice) have reduced mucosal CD103(+)CD11b(+) DC and altered T cell differentiation to protein antigen. The influence of CD103(+)CD11b(+) DC on oral infection with the gastrointestinal pathogen Salmonella, however, is poorly understood and is investigated here. We show that, despite being infected with Salmonella, CD11c-cre.lrf4 mice (called Cre(+) mice) conserve the reduction in CD103(+)CD11b(+) DC observed in naive Cre(+) mice, particularly in the mesenteric lymph nodes (MLN) but also in the siLP at day 3 post infection. Moreover, Salmonella-infected Cre(+) mice have a similar bacterial burden in intestinal tissues (siLP, MLN and Peyer's patches) as well as the spleen compared to infected Cre-controls. The T cell compartment, including the frequency of IFN-gamma and IL-17-producing T cells, is not altered in intestinal tissues of Salmonella-infected Cre(+) mice relative to infected Cre-controls. In addition, no difference between infected Cre(+) and Cre-mice was observed in either the concentration of IL-6 or IL-17 in whole tissue lysates of siLP, MLN or Peyer's patches or in the serum concentration of Salmonella-specific IgG and IgM. Overall the data suggest that the reduction of CD103(+)CD11b(+) DC in Cre(+) mice has little if any impact on Salmonella burden in infected tissues or eliciting effector functions important in host survival at later stages of the infection. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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- Goffo, Elisa, et al.
(author)
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Company for the Ultra-high Density, Ultra-short Period Sub-Earth GJ 367 b: Discovery of Two Additional Low-mass Planets at 11.5 and 34 Days
- 2023
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In: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8213 .- 2041-8205. ; 955:1
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Journal article (peer-reviewed)abstract
- GJ 367 is a bright (V ≈ 10.2) M1 V star that has been recently found to host a transiting ultra-short period sub-Earth on a 7.7 hr orbit. With the aim of improving the planetary mass and radius and unveiling the inner architecture of the system, we performed an intensive radial velocity follow-up campaign with the HARPS spectrograph—collecting 371 high-precision measurements over a baseline of nearly 3 yr—and combined our Doppler measurements with new TESS observations from sectors 35 and 36. We found that GJ 367 b has a mass of M b = 0.633 ± 0.050 M ⊕ and a radius of R b = 0.699 ± 0.024 R ⊕, corresponding to precisions of 8% and 3.4%, respectively. This implies a planetary bulk density of ρ b = 10.2 ± 1.3 g cm−3, i.e., 85% higher than Earth’s density. We revealed the presence of two additional non-transiting low-mass companions with orbital periods of ∼11.5 and 34 days and minimum masses of M c sin i c = 4.13 ± 0.36 M ⊕ and M d sin i d = 6.03 ± 0.49 M ⊕, respectively, which lie close to the 3:1 mean motion commensurability. GJ 367 b joins the small class of high-density planets, namely the class of super-Mercuries, being the densest ultra-short period small planet known to date. Thanks to our precise mass and radius estimates, we explored the potential internal composition and structure of GJ 367 b, and found that it is expected to have an iron core with a mass fraction of 0.91 − 0.23 + 0.07 . How this iron core is formed and how such a high density is reached is still not clear, and we discuss the possible pathways of formation of such a small ultra-dense planet.
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- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 19. |
- Jornvall, H, et al.
(author)
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Pharmacogenetics of the alcohol dehydrogenase system
- 2000
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In: Pharmacology. - : S. Karger AG. - 0031-7012 .- 1423-0313. ; 61:3, s. 184-191
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Journal article (peer-reviewed)abstract
- Alcohol dehydrogenase (ADH) constitutes a complex enzyme system with different forms and extensive multiplicity. A combination of constant and variable properties regarding function, multiplicity and structure of ADH is highlighted for the human system and extended to ADH forms in general. Future perspectives suggest continued studies in specific directions for distinction of metabolic, regulatory and pharmacogenetic roles of ADH.
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| 21. |
- Kalra, Mannudeep K., et al.
(author)
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Sinogram-Affirmed Iterative Reconstruction of Low-Dose Chest CT: Effect on Image Quality and Radiation Dose
- 2013
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In: American Journal of Roentgenology. - : American Roentgen Ray Society (ARRS). - 0361-803X .- 1546-3141. ; 201:2, s. W235-W244
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Journal article (peer-reviewed)abstract
- OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of chest CT acquired with 65% radiation dose reduction.SUBJECTS AND METHODS. In this prospective study involving 24 patients (11 women and 13 men; mean [+/- SD] age, 66 +/- 10 years), two scan series were acquired using 100 and 40 Quality Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The 40 Quality Reference mAs CT projection data were reconstructed with FBP and four settings of Safire (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40 Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation by two thoracic radiologists for number and location of lesions, lesion size, lesion margins, visibility of small structures and fissures, and diagnostic confidence. Objective noise and CT values were measured in thoracic aorta for each image series, and the noise power spectrum was assessed. Data were analyzed with analysis of variance and Wilcoxon signed rank tests.RESULTS. All 186 lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic confidence on SAFIRE images was higher than that for FBP images. Except for the minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 +/- 6.1 SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP images (28.5 +/- 8.1 SD of HU) (p andlt; 0.001). Noise power spectra were identical for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE settings.CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the radiation exposure by approximately 65% without losing diagnostic information in chest CT.
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| 23. |
- Oonk, Maaike H. M., et al.
(author)
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Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node : Results of GROINSS-V II
- 2021
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In: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 39:32, s. 3623-3632
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Journal article (peer-reviewed)abstract
- PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (<= 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
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| 27. |
- Venneri, F., et al.
(author)
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The analysis of the thorium-fueled modular helium-cooled reactor
- 2009
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In: 2008 Proceedings of the 4th International Topical Meeting on High Temperature Reactor Technology, HTR 2008. - 9780791848548 ; , s. 385-390
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Conference paper (peer-reviewed)abstract
- The potential of thorium fertile fuel has been evaluated for a graphite-moderated MHR (Modular Helium Reactor) from the perspective of a self-sustainable U233-Th fuel cycle in the MHR. The 3-D core analyses have been performed with the thermal-hydraulic-coupled computer code systems (HELIOS-MASTER). The feasibility of a self-sustainable U233-Th fuel cycle in MHR was evaluated for a simplified equilibrium fuel cycle. A mixed oxide fuel (ThO2-UO2) was used. Whole-core analysis was performed with the MASTER code for various core configurations. In the core analysis, a 3-batch radial fuel shuffling scheme was adopted to find an equilibrium fuel cycle. Three types of fuel blocks were considered: a homogeneous fuel arrangement and two seed-blanket arrangements. It was found that a near self-sustainable U233-Th fuel cycle (conversion ratio=0.95̃0.97) is feasible for the MHRs with the appropriate U-233 and Th-232 loadings. To achieve a high conversion ratio while maintaining a long cycle length, it is essential to maximize the thorium loading (̃30 tons) and at the same time soften the neutron spectrum to achieve sufficient reactivity. In order to achieve conversion ratios over 0.95 and an 18-month cycle length, the moderator volume needs to be increased with respect to the regular MHR design. Also, removing the inner graphite reflectors increases noticeably the core performance in terms of the conversion ratio and cycle length. A special seed-blanket block configuration (ISB, with seed and blanket fuels in the inner and outer regions of a block, respectively) provides a superior conversion ratio with respect to a homogeneously fueled block, whereas reversing the placement of seed and blanket in the ISB block configuration (with seed fuels in the outer zone) results in a worse performance. In the case of the U233-Th fuel cycle, the fissile (U233+U235) fraction in the discharged fuel is almost 90%. Denaturing of the uranium vector in the self-sustainable U233-Th fuel was investigated by adding 10% LEU in the fuel, to make the initial fissile fraction ̃20.5%. Neutronic analysis of the operation with denatured fuel reveals that the conversion ratio is substantially reduced and the available cycle length is much shorter.
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