| 11. |
- Anåker, Anna, et al.
(author)
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A comparative study of patients' activities and interactions in a stroke unit before and after reconstruction-The significance of the built environment
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 12:7, s. Article no e0177477-
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Journal article (peer-reviewed)abstract
- Early mobilization and rehabilitation, multidisciplinary stroke expertise and comprehensive therapies are fundamental in a stroke unit. To achieve effective and safe stroke care, the physical environment in modern stroke units should facilitate the delivery of evidence-based care. Therefore, the purpose of this study was to explore patients' activities and interactions in a stroke unit before the reconstruction of the physical environment, while in a temporary location and after reconstruction. This case study examined a stroke unit as an integrated whole. The data were collected using a behavioral mapping technique at three different time points: in the original unit, in the temporary unit and in the new unit. A total of 59 patients were included. The analysis included field notes from observations of the physical environment and examples from planning and design documents. The findings indicated that in the new unit, the patients spent more time in their rooms, were less active, and had fewer interactions with staff and family than the patients in the original unit. The reconstruction involved a change from a primarily multi-bed room design to single-room accommodations. In the new unit, the patients' lounge was located in a far corner of the unit with a smaller entrance than the patients' lounge in the old unit, which was located at the end of a corridor with a noticeable entrance. Changes in the design of the stroke unit may have influenced the patients' activities and interactions. This study raises the question of how the physical environment should be designed in the future to facilitate the delivery of health care and improve outcomes for stroke patients. This research is based on a case study, and although the results should be interpreted with caution, we strongly recommend that environmental considerations be included in future stroke guidelines.
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| 12. |
- Firth, N., et al.
(author)
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Safety and efficacy of recovery-promoting drugs for motor function after stroke: A systematic review of randomized controlled trials
- 2019
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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 51:5, s. 319-330
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Journal article (peer-reviewed)abstract
- - Objective: To investigate the efficacy and safety of drug interventions to promote motor recovery poststroke. Data sources: CENTRAL, CINAHL, Embase, MEDLINE, SCOPUS and Web of Science. Study selection: Published human randomized controlled trials in which the primary intervention was a drug administered to promote motor recovery poststroke, vs placebo. Data extraction: Standardized pro forma used to extract safety and efficacy data; Cochrane Collaboration risk of bias assessment tool performed to assess risk of bias. Data synthesis: Fifty randomized controlled trials from 4,779 citations were included. An overall trend of high risk of attrition (n=27) and reporting bias (n=36) was observed. Twenty-eight different drug interventions were investigated, 18 of which demonstrated statistically significant results favouring increased motor recovery compared with control intervention. Forty-four studies measured safety; no major safety concerns were reported. Conclusion: Candidate drug interventions promoting motor recovery post-stroke were identified, specifically selective serotonin reuptake inhibitors and levodopa; however, the high risk of bias in many trials is concerning. Drugs to improve motor function remain an important area of enquiry. Future research must focus on establishing the right drug intervention to be administered at an optimal dose and time, combined with the most effective adjuvant physical therapy to drive stroke recovery. © 2019 Foundation of Rehabilitation Information.
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| 13. |
- Fischer, David, et al.
(author)
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Comparison of control approaches for variable speed air source heat pumps considering time variable electricity prices and PV
- 2017
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In: Applied Energy. - : Elsevier. - 0306-2619 .- 1872-9118. ; 204, s. 93-105
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Journal article (peer-reviewed)abstract
- The influence of different control strategies and boundary conditions on heat pump system performance are investigated in this study and the trade-off between complexity and performance of different controllers is addressed. For this purpose five different control approaches for a variable speed air source heat pump in a multi family house are compared for three different use-cases. The used controls differ in complexity and the use of external input data like price and weather forecasts. The use-cases are: Constant electricity prices, time variable electricity prices and PV self-consumption. Four different rule-based controllers are compared to a convex MPC approach, presented in this work. Results show that the MPC approach reduces annual operating cost by 6–11% for constant electricity prices and 6–16% in the case of variable electricity prices. Rule-based approaches lead to cost reductions of 2–4%. MPC could increases PV self-consumption from 56% to 58% up to 64–71%. The rule base approaches are found computationally less demanding and easier to design. However fine-tuning has been considerable work and with changing boundary conditions rules had to be readjusted. It showed that increasing thermal storage without MPC is not beneficial and optimised controls are a prerequisite to benefit from increased storage sizes.
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| 14. |
- Muller, C., et al.
(author)
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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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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:9
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Journal article (peer-reviewed)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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| 15. |
- Shannon, Michelle M., et al.
(author)
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Can the physical environment itself influence neurological patient activity?
- 2019
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In: Disability and Rehabilitation. - : Informa UK Limited. - 1464-5165 .- 0963-8288. ; 41:10, s. 1177-1189
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate if a changed physical environment following redesign of a hospital ward influenced neurological patient physical and social activity. Methods: A “before and after” observational design was used that included 17 acute neurological patients pre-move (median age 77 (IQR 69–85) years Ward A and 20 post-move (median age 70 (IQR 57–81) years Ward B. Observations occurred for 1 day from 08.00–17.00 using Behavioral Mapping of patient physical and social activity, and location of that activity. Staff and ward policies remained unchanged throughout. An Environmental Description Checklist of each ward was also completed. Results: Behavioral Mapping was conducted pre-/post-move with a total of 801 Ward A and 918 Ward B observations. Environmental Description Checklists showed similarities in design features in both neurological wards with similar numbers of de-centralized nursing stations, however there were more single rooms and varied locations to congregate in Ward B (30% more single-patient rooms and separate allied health therapy room). Patients were alone >60% of time in both wards, although there was more in bed social activity in Ward A and more out of bed social activity in Ward B. There were low amounts of physical activity outside of patient rooms in both wards. Significantly more physical activity occurred in Ward B patient rooms (median = 47%, IQR 14–74%) compared to Ward A (median = 2% IQR 0–14%), Wilcoxon Rank Sum test z = −3.28, p = 0.001. Conclusions: Overall, patient social and physical activity was low, with little to no use of communal spaces. However we found more physical activity in patient rooms in the Ward B environment. Given the potential for patient activity to drive brain reorganization and repair, the physical environment should be considered an active factor in neurological rehabilitation and recovery.Implications for Rehabilitation Clinicians should include consideration of the impact of physical environment on physical and social activity of neurological patients when designing therapeutic rehabilitation environments. Despite architectural design intentions patient and social activity opportunities can be limited. Optimal neurological patient neuroplasticity and recovery requires sufficient environmental challenge, however current hospital environments for rehabilitation do not provide this.
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| 16. |
- Siwowska, K., et al.
(author)
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Therapeutic Potential of Sc-47 in Comparison to Lu-177 and Y-90: Preclinical Investigations
- 2019
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:8
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Journal article (peer-reviewed)abstract
- Targeted radionuclide therapy with Lu-177- and Y-90-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. Sc-47 is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy beta(-)particles. In this study, Sc-47 was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of Lu-17-folate and Y-90-folate, respectively. In vitro, Sc-47-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to Lu-177-folate, but Y-90-folate was more potent at equal activities due to the higher energy of emitted beta(-)particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (similar to 21 Gy) when treated with Sc-47-folate (12.5 MBq), Lu-177-folate (10 MBq), and Y-90-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, Sc-47 is likely to be comparable to Lu-177 when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with Sc-44 or Sc-43 as a diagnostic match, enabling the realization of radiotheragnostics in future.
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| 17. |
- Sundlöv, Anna, et al.
(author)
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Feasibility of simplifying renal dosimetry in Lu-177 peptide receptor radionuclide therapy
- 2018
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In: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1
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Journal article (peer-reviewed)abstract
- Background: Recently, Lu-177-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done. The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours. As part of a clinical trial on Lu-177-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses. Results: In general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD. Conclusions: Performing one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.
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| 18. |
- Sundlöv, Anna, et al.
(author)
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Individualised Lu-177-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry
- 2017
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 44:9, s. 1480-1489
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Journal article (peer-reviewed)abstract
- Purpose To present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED). Method Treatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 +/- 2 Gy (alpha/beta = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 +/- 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR). Results Fifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function. Conclusions Individualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.
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| 19. |
- Wagner, AK, et al.
(author)
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Expression of CD226 is associated to but not required for NK cell education
- 2017
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15627-
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Journal article (peer-reviewed)abstract
- DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226−/− mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.
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| 20. |
- Yang, Zhenlin, et al.
(author)
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Structural basis of ligand binding modes at the neuropeptide Y Y-1 receptor
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 556:7702, s. 520-524
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Journal article (peer-reviewed)abstract
- Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology(1,2). The NPY-Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y-1, Y-2, Y-4 and Y-5 receptors, with different affinity and selectivity(3). NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y-1 receptor (Y1R)(4). A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity(4), tumour(1) and bone loss(5). However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability(6). Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 angstrom resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors.
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