| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Grieser, M., et al.
(författare)
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Storage ring at HIE-ISOLDE Technical design report
- 2012
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Ingår i: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 207:1, s. 1-117
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Forskningsöversikt (refereegranskat)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 3. |
- Grieser, M., et al.
(författare)
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Storage ring at HIE-ISOLDE
- 2012
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Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 207:1, s. 1-117
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Tidskriftsartikel (refereegranskat)abstract
- We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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| 4. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 5. |
- Lestinsky, M., et al.
(författare)
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Physics book: CRYRING@ESR
- 2016
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Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
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Forskningsöversikt (refereegranskat)abstract
- The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
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| 6. |
- Opheim, G., et al.
(författare)
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7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice
- 2021
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:7, s. 327-341
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Tidskriftsartikel (refereegranskat)abstract
- Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
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| 7. |
- Staude, I. R., et al.
(författare)
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Directional turnover towards larger-ranged plants over time and across habitats
- 2022
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 466-82
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Tidskriftsartikel (refereegranskat)abstract
- Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.
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| 8. |
- Eddy, Tyler D., et al.
(författare)
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Energy Flow Through Marine Ecosystems : Confronting Transfer Efficiency
- 2021
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 36:1, s. 76-86
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Forskningsöversikt (refereegranskat)abstract
- Transfer efficiency is the proportion of energy passed between nodes in food webs. It is an emergent, unitless property that is difficult to measure, and responds dynamically to environmental and ecosystem changes. Because the consequences of changes in transfer efficiency compound through ecosystems, slight variations can have large effects on food availability for top predators. Here, we review the processes controlling transfer efficiency, approaches to estimate it, and known variations across ocean biomes. Both process-level analysis and observed macro-scale variations suggest that ecosystem-scale transfer efficiency is highly variable, impacted by fishing, and will decline with climate change. It is important that we more fully resolve the processes controlling transfer efficiency in models to effectively anticipate changes in marine ecosystems and fisheries resources.
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| 9. |
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| 10. |
- Bernhardt, A. M., et al.
(författare)
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A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases
- 2023
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi) genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 11. |
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| 12. |
- Kananen, L, et al.
(författare)
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Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
- 2023
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Ingår i: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:1, s. 85-103
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Tidskriftsartikel (refereegranskat)abstract
- Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
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| 13. |
- Kananen, L, et al.
(författare)
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Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 6139-
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Tidskriftsartikel (refereegranskat)abstract
- Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual’s subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
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| 14. |
- Powers, M. B., et al.
(författare)
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A Randomized Controlled Trial of Animated Versus Live Action Virtual Reality Therapy for Anxiety & Pain in a Level I Trauma Center
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- While virtual reality exposure therapy (VRET) shows promise as a treatment for anxiety and pain (Powers & Emmelkamp, 2008), many users complain that computer-generated virtual reality (VR) stimuli appear unrealistic, eccentric, and too much like a video game (Kwon, Powell, & Chalmers, 2013). Historically, programmers using video game assets and computer-generated imagery (CGI) created VR content. While CGI can be used to make intricate virtual environments, unless there is a team of expert digital artists, the virtual stimulus may look unrealistic and exhibit a number of graphical glitches that could prove distracting in therapy. Furthermore, CGI often suffers from the uncanny valley effect, where CGI representations of people are perceived as unsettling as the representations become more lifelike. Thus, the only method to overcome the uncanny valley effect is to present the VR as less realistic (CGI) or photorealistic. In addition, current CGI VR packages are expensive and difficult to implement in widespread medical settings. Recently, however, an exciting alternative to traditional computer-generated VR has emerged: 360-Degree 3-D HD Video VR (Live Action). The benefit of Live Action VR as opposed to CGI VR is that it is photorealistic and doesn’t cause the uncanny valley effect of CGI. In addition, the projected cost of the end product is approximately $500 and delivered using a portable VR headset. In this RCT, participants in a Level I Trauma Center reporting pain (N = 78) were randomized to waitlist, 10-minutes of CGI VR, or 10-minutes of Live Action VR. Consistent with prediction, both VR conditions showed greater reduction in anxiety relative to waitlist (p < .05). However, there was no difference between the conditions. The two VR conditions also showed significantly greater reductions in pain (p < .001) and pain interference (p < .001) relative to the waitlist with no differences between conditions. As expected, participants rated Live Action VR significantly more realistic than CGI VR (p < .001) and reported a greater sense of being in the virtual world (p < .05). Finally, 92% of participants in the waitlist preferred to view the Live Action VR.
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| 15. |
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| 16. |
- Cumming, T. B., et al.
(författare)
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Early Mobilization After Stroke Is Not Associated With Cognitive Outcome Findings From AVERT
- 2018
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 49:9, s. 2147-2154
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose We aimed to determine whether early mobilization after stroke affects subsequent cognitive function. Methods-AVERT (A Very Early Rehabilitation Trial) was an international, 56-site, phase 3 randomized controlled trial, conducted from 2006 to 2015. Participants were included if they were aged 18+, presented within 24 hours of stroke, and satisfied physiological limits for blood pressure, heart rate, and temperature. Participants were randomized to receive either usual stroke unit care or very early and more frequent mobilization in addition to usual stroke unit care. The Montreal Cognitive Assessment, scored 0 to 30, was introduced as a 3-month outcome during 2008. Results-Of the 2104 patients included in AVERT, 317 were assessed before the Montreal Cognitive Assessment's introduction. Of the remaining 1787, 1189 (66.5%) had complete Montreal Cognitive Assessment data, 456 (25.5%) had partially or completely missing data, 136 (7.6%) had died, and 6 (0.3%) were lost to follow-up. In surviving participants with complete data, adjusting for age and stroke severity, total Montreal Cognitive Assessment score was no different in the intervention (n=595; median, 23; interquartile range, 19-26; mean, 21.9; SD, 5.9) and usual care (n=594; median, 23; interquartile range, 19-26; mean, 21.8; SD, 5.9) groups (P=0.68). Conclusions-Exposure to earlier and more frequent mobilization in the acute stage of stroke does not influence cognitive outcome at 3 months. This stands in contrast to the primary outcome from AVERT (modified Rankin Scale), where the intervention group had less favorable outcomes than controls.
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| 17. |
- Hysell, D. L., et al.
(författare)
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Heater-induced ionization inferred from spectrometric airglow measurements
- 2014
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Ingår i: Journal of Geophysical Research A: Space Physics. - 2169-9380. ; 119:3, s. 2038-2045
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Tidskriftsartikel (refereegranskat)abstract
- Spectrographic airglow measurements were made during an ionospheric modification experiment at High Frequency Active Auroral Research Program on 12 March 2013. Artificial airglow enhancements at 427.8, 557.7, 630.0, 777.4, and 844.6 nm were observed. On the basis of these emissions and using a methodology based on the method of Backus and Gilbert (1968, 1970), we estimate the suprathermal electron population and the subsequent equilibrium electron density profile, including contributions from electron impact ionization. We find that the airglow is consistent with heater-induced ionization in view of the spatial intermittency of the airglow.
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| 18. |
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| 19. |
- Muller, C., et al.
(författare)
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Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute
- 2019
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using Lu-177-folate and Lu-177-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by beta over bar -particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
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| 20. |
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| 21. |
- Staude, I. R., et al.
(författare)
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Replacements of small- by large-ranged species scale up to diversity loss in Europe's temperate forest biome
- 2020
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 4, s. 802-808
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Tidskriftsartikel (refereegranskat)abstract
- The loss of biodiversity at the global scale has been difficult to reconcile with observations of no net loss at local scales. Vegetation surveys across European temperate forests show that this may be explained by the replacement of small-ranged species with large-ranged ones, driven by nitrogen deposition. Biodiversity time series reveal global losses and accelerated redistributions of species, but no net loss in local species richness. To better understand how these patterns are linked, we quantify how individual species trajectories scale up to diversity changes using data from 68 vegetation resurvey studies of seminatural forests in Europe. Herb-layer species with small geographic ranges are being replaced by more widely distributed species, and our results suggest that this is due less to species abundances than to species nitrogen niches. Nitrogen deposition accelerates the extinctions of small-ranged, nitrogen-efficient plants and colonization by broadly distributed, nitrogen-demanding plants (including non-natives). Despite no net change in species richness at the spatial scale of a study site, the losses of small-ranged species reduce biome-scale (gamma) diversity. These results provide one mechanism to explain the directional replacement of small-ranged species within sites and thus explain patterns of biodiversity change across spatial scales.
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| 22. |
- Verheyen, Kris, et al.
(författare)
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201 Combining Biodiversity Resurveys across Regions to Advance Global Change Research
- 2017
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:1, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- More and more ecologists have started to resurvey communities sampled in earlier decades to determine long-term shifts in community composition and infer the likely drivers of the ecological changes observed. However, to assess the relative importance of and interactions among multiple drivers, joint analyses of resurvey data from many regions spanning large environmental gradients are needed. In this article, we illustrate how combining resurvey data from multiple regions can increase the likelihood of driver orthogonality within the design and show that repeatedly surveying across multiple regions provides higher representativeness and comprehensiveness, allowing us to answer more completely a broader range of questions. We provide general guidelines to aid the implementation of multiregion resurvey databases. In so doing, we aim to encourage resurvey database development across other community types and biomes to advance global environmental change research.
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| 23. |
- Andersson, Jonas, 1975-, et al.
(författare)
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Artificial intelligence and the medical physics profession-A Swedish perspective
- 2021
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Ingår i: Physica Medica-European Journal of Medical Physics. - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 88, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a continuous and dynamic discussion on artificial intelligence (AI) in present-day society. AI is expected to impact on healthcare processes and could contribute to a more sustainable use of resources allocated to healthcare in the future. The aim for this work was to establish a foundation for a Swedish perspective on the potential effect of AI on the medical physics profession. Materials and methods: We designed a survey to gauge viewpoints regarding AI in the Swedish medical physics community. Based on the survey results and present-day situation in Sweden, a SWOT analysis was performed on the implications of AI for the medical physics profession. Results: Out of 411 survey recipients, 163 responded (40%). The Swedish medical physicists with a professional license believed (90%) that AI would change the practice of medical physics but did not foresee (81%) that AI would pose a risk to their practice and career. The respondents were largely positive to the inclusion of AI in educational programmes. According to self-assessment, the respondents' knowledge of and workplace preparedness for AI was generally low. Conclusions: From the survey and SWOT analysis we conclude that AI will change the medical physics profession and that there are opportunities for the profession associated with the adoption of AI in healthcare. To overcome the weakness of limited AI knowledge, potentially threatening the role of medical physicists, and build upon the strong position in Swedish healthcare, medical physics education and training should include learning objectives on AI.
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| 24. |
- Baum, R. P., et al.
(författare)
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First-in-Humans Application of Tb-161: A Feasibility Study Using Tb-161-DOTATOC
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 62:10, s. 1391-1397
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Tidskriftsartikel (refereegranskat)abstract
- Tb-161 has decay properties similar to those of Lu-177 but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply Tb-161 in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of Tb-161-DOTATOC. Methods: Tb-161 was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of Tb-161-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar g-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of Tb-161-DOTATOC. Results: The radiolabeling of DOTATOC with Tb-161 was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of Tb-161-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of Tb-161-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of Tb-161-DOTATOC using g-scintigraphy and SPECT/CT. On the basis of this essential first step in translating Tb-161 to clinics, further efforts will be directed toward the application of Tb-161 for therapeutic purposes.
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| 25. |
- Benjegård, S A, et al.
(författare)
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Evaluation of three gamma detectors for intraoperative detection of tumors using 111In-labeled radiopharmaceuticals.
- 1999
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 40:12, s. 2094-101
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Tidskriftsartikel (refereegranskat)abstract
- Attempts to detect tumors with intraoperative scintillation using tumor-binding radiopharmaceuticals have intensified recently. In some cases previously unknown lesions were found, but in most cases no additional lesions were detected. In this study the physical characteristics of three detector systems and their ability to detect tumors through accumulation of an 111In-labeled radiopharmaceutical were investigated. The first was a sodium iodide (NaI[TI]) detector; the second, a cesium iodide (CsI[TI]) detector; and the third, a cadmium telluride (CdTe) detector.
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| 26. |
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| 27. |
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| 28. |
- De Frenne, Pieter, et al.
(författare)
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Microclimate moderates plant responses to macroclimate warming
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:46, s. 18561-18565
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Tidskriftsartikel (refereegranskat)abstract
- Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., thermophilization of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that climatic lags may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity.
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| 29. |
- De Frenne, Pieter, et al.
(författare)
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Plant movements and climate warming : intraspecific variation in growth responses to nonlocal soils
- 2014
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 202:2, s. 431-441
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Tidskriftsartikel (refereegranskat)abstract
- Most range shift predictions focus on the dispersal phase of the colonization process. Because moving populations experience increasingly dissimilar nonclimatic environmental conditions as they track climate warming, it is also critical to test how individuals originating from contrasting thermal environments can establish in nonlocal sites. We assess the intraspecific variation in growth responses to nonlocal soils by planting a widespread grass of deciduous forests (Milium effusum) into an experimental common garden using combinations of seeds and soil sampled in 22 sites across its distributional range, and reflecting movement scenarios of up to 1600km. Furthermore, to determine temperature and forest-structural effects, the plants and soils were experimentally warmed and shaded. We found significantly positive effects of the difference between the temperature of the sites of seed and soil collection on growth and seedling emergence rates. Migrant plants might thus encounter increasingly favourable soil conditions while tracking the isotherms towards currently colder' soils. These effects persisted under experimental warming. Rising temperatures and light availability generally enhanced plant performance. Our results suggest that abiotic and biotic soil characteristics can shape climate change-driven plant movements by affecting growth of nonlocal migrants, a mechanism which should be integrated into predictions of future range shifts.
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| 30. |
- De Pauw, Karen, et al.
(författare)
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Taxonomic, phylogenetic and functional diversity of understorey plants respond differently to environmental conditions in European forest edges
- 2021
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 109:7, s. 2629-2648
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Tidskriftsartikel (refereegranskat)abstract
- Forest biodiversity world-wide is affected by climate change, habitat loss and fragmentation, and today 20% of the forest area is located within 100 m of a forest edge. Still, forest edges harbour a substantial amount of terrestrial biodiversity, especially in the understorey. The functional and phylogenetic diversity of forest edges have never been studied simultaneously at a continental scale, in spite of their importance for the forests' functioning and for communities' resilience to future change.We assessed nine metrics of taxonomic, phylogenetic and functional diversity of understorey plant communities in 225 plots spread along edge-to-interior gradients in deciduous forests across Europe. We then derived the relative effects and importance of edaphic, stand and landscape conditions on the diversity metrics.Here, we show that taxonomic, phylogenetic and functional diversity metrics respond differently to environmental conditions. We report an increase in functional diversity in plots with stronger microclimatic buffering, in spite of their lower taxonomic species richness. Additionally, we found increased taxonomic species richness at the forest edge, but in forests with intermediate and high openness, these communities had decreased phylogenetic diversity.Functional and phylogenetic diversity revealed complementary and important insights in community assembly mechanisms. Several environmental filters were identified as potential drivers of the patterns, such as a colder macroclimate and less buffered microclimate for functional diversity. For phylogenetic diversity, edaphic conditions were more important. Interestingly, plots with lower soil pH had decreased taxonomic species richness, but led to increased phylogenetic diversity, challenging the phylogenetic niche conservatism concept.Synthesis. Taxonomic, phylogenetic and functional diversity of understorey communities in forest edges respond differently to environmental conditions, providing insight into different community assembly mechanisms and their interactions. Therefore, it is important to look beyond species richness with phylogenetic and functional diversity approaches when focusing on forest understorey biodiversity.
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| 31. |
- De Schuyter, Wim, et al.
(författare)
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Declining potential nectar production of the herb layer in temperate forests under global change
- 2024
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Ingår i: Journal of Ecology. - 0022-0477 .- 1365-2745. ; 112:4, s. 832-847
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Tidskriftsartikel (refereegranskat)abstract
- Wild pollinators are crucial for ecosystem functioning and human food production and often rely on floral resources provided by different (semi-) natural ecosystems for survival. Yet, the role of European forests, and especially the European forest herb layer, as a potential provider of floral resources for pollinators has scarcely been quantified.In this study, we measured the potential nectar production (PNP) of the forest herb layer using resurvey data across 3326 plots in temperate forests in Europe, with an average time interval of 41 years between both surveys in order to assess (i) the importance of the forest herb layer in providing nectar for wild pollinators, (ii) the intra-annual variation of PNP, (iii) the overall change in PNP between survey periods and (iv) the change in intra-annual variation of PNP between survey periods. The PNP estimates nectar availability based on the relative cover of different plant species in the forest herb layer. Although PNP overestimates actual nectar production, relative differences amongst plots provide a valid and informative way to analyse differences across time and space.Our results show that the forest herb layer has a large potential for providing nectar for wild pollinator communities, which is greatest in spring, with an average PNP of almost 16 g sugar/m2/year. However, this potential has drastically declined (mean plot-level decline >24%).Change in light availability, associated with shifts in canopy structure and canopy composition, is the key driver of temporal PNP changes.Synthesis. Our study shows that if management activities are carefully planned to sustain nectar-producing plant species for wild pollinators, European forest herb layers and European forests as a whole can play key roles in sustaining wild pollinator populations.
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| 32. |
- Doherty, Gareth G., et al.
(författare)
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Synthesis of Uronic Acid 1-Azasugars as Putative Inhibitors of α-Iduronidase, β-Glucuronidase and Heparanase
- 2023
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Ingår i: ChemBioChem. - : Wiley-VCH Verlagsgesellschaft. - 1439-4227 .- 1439-7633. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- 1-Azasugar analogues of l-iduronic acid (l-IdoA) and d-glucuronic acid (d-GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding α-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d- or l-arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l-IdoA-configured 8 moderately inhibited β-glucuronidase (β-GLU). The d-GlcA-configured 9 was a potent inhibitor of β-GLU and a moderate inhibitor of the endo-β-glucuronidase heparanase. Co-crystallization of 9 with heparanase revealed that the endocyclic nitrogen of 9 forms close interactions with both the catalytic acid and catalytic nucleophile.
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| 33. |
- Eigler, Christopher, et al.
(författare)
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Radiolabeled Somatostatin Receptor Antagonist Versus Agonist for Peptide Receptor Radionuclide Therapy in Patients with Therapy-Resistant Meningioma: PROMENADE Phase 0 Study
- 2024
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Ingår i: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667. ; 65:4, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Our primary aim was to compare the therapeutic index (tumor-to- bone marrow and tumor -to -kidney absorbed -dose ratios) of the new radiolabeled somatostatin receptor antagonist [ 177 Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [ 177 Lu]Lu-DOTATOC in the same patients with progressive, standard therapy -refractory meningioma. Methods: In this prospective, singlecenter, open -label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [ 177 Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m 2 3 body surface area) of [ 177 Lu]Lu-DOTA-JR11 at an interval of 10 6 1 wk. In total, 1 [ 177 Lu]Lu-DOTATOC and 2-3 [ 177 Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor -to -organ absorbed -dose ratios (3 -dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [ 177 Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [ 177 Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3- 5.3 Gy) for [ 177 Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [ 177 Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed -dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor -to -kidney absorbed -dose ratio with [ 177 Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [ 177 Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [ 177 Lu]Lu- DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [ 177 Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [ 177 Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [ 177 Lu]Lu-DOTA-JR11 are warranted in meningioma patients.
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| 34. |
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| 35. |
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| 36. |
- Frolov, V.L., Erukhimov, L.M., Komrakov, G.P., Sergeev, E.N., Thidé, B., Bernhardt, P. Wagner, L.S., Goldstein, J.A., Selcher, G.
(författare)
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On the Enhancement of the BUM SEE Feature by Additional Pulse Heating of the onospheric Plasma
- 1997
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Ingår i: Radiophysics and Quantum Electronics. ; 40, s. 371-386
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Tidskriftsartikel (refereegranskat)
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| 37. |
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| 38. |
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| 39. |
- Hattermann, D., et al.
(författare)
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Geese are overlooked dispersal vectors for vascular plants in archipelago environments
- 2019
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Ingår i: Journal of Vegetation Science. - : Wiley-Blackwell. - 1100-9233 .- 1654-1103. ; 30:3, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- Question: We addressed the importance of gut-mediated dispersal by greylag geese for vascular plants in archipelago environments and asked: (a) What proportion of the local species pool is dispersed by geese? (b) Which plant traits characterize species dispersed by geese? (c) Which plant communities are likely to benefit from endozoochory by geese?. Location: Three Swedish Baltic archipelagos. Methods: Goose droppings were collected on 45 islands. Plants germinating from the droppings represent the endozoochorous species pool (ESP). On 108 islands, the presence of vascular plants was recorded in each habitat. These species represent the island species pool (ISP). Differences in functional traits between ESP and ISP were expressed as effect sizes and tested using meta-regressions. Using indicator species analyses and indicator species for managed semi-natural grasslands, we identified the primary habitats of the ESP. Results: Geese dispersed viable diaspores of 97 plant species, which represents 22% of the ISP. Most ESP species were typical for small islands. Geese dispersed a higher proportion of graminoids and less woody plants, higher proportions of chamaephytes and therophytes and less phanerophytes; annuals and bi-annuals were significantly overrepresented. On average, seed volume of the ESP was 95% smaller than that of the ISP. About 51% of all ESP species were dispersed in at least two archipelagos. Geese showed a bias towards species of rocky shore habitats. Conclusion: Geese potentially disperse large amounts of diaspores of many terrestrial island plant species. Through their feeding behaviour, geese select species with certain suites of traits from the regional species pool. Plant dispersal by geese may benefit plants species of rocky shores, but species of formerly managed semi-natural grasslands may also find refuge sites on epilittoral shores after goose-mediated dispersal. The relative importance of geese as dispersal vectors may increase under on-going land-use changes and cessation of grazing networks.
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| 40. |
- Kölby, Lars, 1963, et al.
(författare)
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A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
- 2001
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Ingår i: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
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Tidskriftsartikel (refereegranskat)abstract
- A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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| 41. |
- Kölby, Lars, 1963, et al.
(författare)
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Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1383-8
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Tidskriftsartikel (refereegranskat)abstract
- The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.
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| 42. |
- Levin, Johannes, et al.
(författare)
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α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
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| 43. |
- Lipoma, Lucrecia, et al.
(författare)
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No general support for functional diversity enhancing resilience across terrestrial plant communities
- 2024
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Ingår i: Global Ecology and Biogeography. - : John Wiley & Sons. - 1466-822X .- 1466-8238.
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Forskningsöversikt (refereegranskat)abstract
- Aim: Understanding the mechanisms promoting resilience in plant communities is crucial in times of increasing disturbance and global environmental change. Here, we present the first meta-analysis evaluating the relationship between functional diversity and resilience of plant communities. Specifically, we tested whether the resilience of plant communities is positively correlated with interspecific trait variation (following the niche complementarity hypothesis) and the dominance of acquisitive and small-size species (following the mass ratio hypothesis), and for the context-dependent effects of ecological and methodological differences across studies.Location: Global.Time Period: 2004–2021.Major Taxa Studied: Vascular plants.Methods: We compiled a dataset of 69 independent sites from 26 studies that have quantified resilience. For each site, we calculated functional diversity indices based on the floristic composition and functional traits of the plant community (obtained from the TRY database) which we correlated with resilience of biomass and floristic composition. After transforming correlation coefficients to Fisher's Z-scores, we conducted a hierarchical meta-analysis, using a multilevel random-effects model that accounted for the non-independence of multiple effect sizes and the effects of ecological and methodological moderators. Results: In general, we found no positive functional diversity–resilience relationships of grand mean effect sizes. In contrast to our expectations, we encountered a negative relationship between resilience and trait variety, especially in woody ecosystems, whereas there was a positive relationship between resilience and the dominance of acquisitive species in herbaceous ecosystems. Finally, the functional diversity–resilience relationships were strongly affected by both ecological (biome and disturbance properties) and methodological (temporal scale, study design and resilience metric) characteristics. Main Conclusions: We rejected our hypothesis of a general positive functional diversity–resilience relationship. In addition to strong context dependency, we propose that idiosyncratic effects of single resident species present in the communities before the disturbances and biological legacies could play major roles in the resilience of terrestrial plant communities.
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| 44. |
- Lipson-Smith, R., et al.
(författare)
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Built environments for inpatient stroke rehabilitation services and care : A systematic literature review
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify, appraise and synthesise existing design evidence for inpatient stroke rehabilitation facilities; to identify impacts of these built environments on the outcomes and experiences of people recovering from stroke, their family/caregivers and staff. Design A convergent segregated review design was used to conduct a systematic review. Data sources Ovid MEDLINE, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature were searched for articles published between January 2000 and November 2020. Eligibility criteria for selecting studies Qualitative, quantitative and mixed-methods studies investigating the impact of the built environment of inpatient rehabilitation facilities on stroke survivors, their family/caregivers and/or staff. Data extraction and synthesis Two authors separately completed the title, abstract, full-text screening, data extraction and quality assessment. Extracted data were categorised according to the aspect of the built environment explored and the outcomes reported. These categories were used to structure a narrative synthesis of the results from all included studies. Results Twenty-four articles were included, most qualitative and exploratory. Half of the included articles investigated a particular aspect of the built environment, including environmental enrichment and communal areas (n=8), bedroom design (n=3) and therapy spaces (n=1), while the other half considered the environment in general. Findings related to one or more of the following outcome categories: (1) clinical outcomes, (2) patient activity, (3) patient well-being, (4) patient and/or staff safety and (5) clinical practice. Heterogeneous designs and variables of interest meant results could not be compared, but some repeated findings suggest that attractive and accessible communal areas are important for patient activity and well-being. Conclusions Stroke rehabilitation is a unique healthcare context where patient activity, practice and motivation are paramount. We found many evidence gaps that with more targeted research could better inform the design of rehabilitation spaces to optimise care. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 45. |
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| 46. |
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| 47. |
- Muller, C., et al.
(författare)
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Promising Prospects for Sc-44-/Sc-47-Based Theragnostics: Application of Sc-47 for Radionuclide Tumor Therapy in Mice
- 2014
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 55:10, s. 1658-1664
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, Sc-47 has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 key; Ey, 159 key) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of Sc-47 for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: Sc-47 was produced via the Ca-46(n,gamma)Ca-47 -> Sc beta-47 nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the Sc-47 from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. Sc-47-labeled cm10 was tested on folate receptor-positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor-bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either Sc-47-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of Ca-46 resulted in approximately 1.8 GBq of Ca-47, which subsequently decayed to Sc-47. Separation of Sc-47 from Ca-47 was obtained with 80% yield in only 10 min. The Sc-47 was then available in a small volume (-500 pL) of an ammonium acetate/HCI (pH 4.5) solution suitable for direct radiolabeling. Sc-47-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 475ccm10 showed folate receptor-specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received Sc-47-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using Sc-47 for therapeutic purposes. On the basis of our recent results obtained with Sc-44-folate, the present work confirms the applicability of Sc-44/Sc-47 as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.
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| 48. |
- Muller, C., et al.
(författare)
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Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:9, s. 1919-1930
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate Tb-161 (T-1/2=6.89days; E beta(?)(av)=154keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to Lu-177-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.Methods(161)Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100MBq/nmol. Tb-161-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for Lu-177-PSMA-617. The effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. Tb-161-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.Results(161)Tb-PSMA-617 and Lu-177-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to Tb-161-PSMA-617 as compared to the effect obtained with the same activities of Lu-177-PSMA-617 over the whole investigated concentration range. Treatment of mice with Tb-161-PSMA-617 (5.0MBq/mouse and 10MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65days) compared to untreated control animals (19days). Therapy studies to compare the effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 indicated the anticipated superiority of Tb-161 over Lu-177.Conclusion(161)Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to Lu-177-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of Tb-161. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of Tb-161-PSMA-617 for the treatment of mCRPC.
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| 49. |
- Nordblad, Erik, 1981-
(författare)
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Opening New Radio Windows and Bending Twisted Beams
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In ground based high frequency (HF) radio pumping experiments, absorption of ordinary (O) mode pump waves energises the ionospheric plasma, producing optical emissions and other effects. Pump-induced or natural kilometre-scale field-aligned density depletions are believed to play a role in self-focussing phenomena such as the magnetic zenith (MZ) effect, i.e., the increased plasma response observed in the direction of Earth's magnetic field. Using ray tracing, we study the propagation of ordinary (O) mode HF radio waves in an ionosphere modified by density depletions, with special attention to transmission through the radio window (RW), where O mode waves convert into the extraordinary (X, or Z) mode. The depletions are shown to shift the position of the RW, or to introduce RWs at new locations. In a simplified model neglecting absorption, we estimate the wave electric field strength perpendicular to the magnetic field at altitudes normally inaccessible. This field could excite upper hybrid waves on small scale density perturbations. We also show how transmission and focussing combine to give stronger fields in some directions, notably at angles close to the MZ, with possible implications for the MZ effect. In a separate study, we consider electromagnetic (e-m) beams with helical wavefronts (i.e., twisted beams), which are associated with orbital angular momentum (OAM). By applying geometrical optics to each plane wave component of a twisted nonparaxial e-m Bessel beam, we calculate analytically the shift of the beam's centre of gravity during propagation perpendicularly and obliquely to a weak refractive index gradient in an isotropic medium. In addition to the so-called Hall shifts expected from paraxial theory, the nonparaxial treatment reveals new shifts in both the transverse and lateral directions. In some situations, the new shifts should be significant also for nearly paraxial beams.
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| 50. |
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