| 71. |
- Silva Barreto, Isabella, et al.
(författare)
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Multiscale Characterization of Embryonic Long Bone Mineralization in Mice
- 2020
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Ingår i: Advanced Science. - : Wiley. - 2198-3844 .- 2198-3844. ; 7:21
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Tidskriftsartikel (refereegranskat)abstract
- Long bone mineralization occurs through endochondral ossification, where a cartilage template mineralizes into bone-like tissue with a hierarchical organization from the whole bone-scale down to sub-nano scale. Whereas this process has been extensively studied at the larger length scales, it remains unexplored at some of the smaller length scales. In this study, the changes in morphology, composition, and structure during embryonic mineralization of murine humeri are investigated using a range of high-resolution synchrotron-based imaging techniques at several length scales. With micro- and nanometer spatial resolution, the deposition of elements and the shaping of mineral platelets are followed. Rapid mineralization of the humeri occurs over approximately four days, where mineral to matrix ratio and calcium content in the most mineralized zone reach adult values shortly before birth. Interestingly, zinc is consistently found to be localized at the sites of ongoing new mineralization. The mineral platelets in the most recently mineralized regions are thicker, longer, narrower, and less aligned compared to those further into the mineralized region. In summary, this study demonstrates a specific spatial distribution of zinc, with highest concentration where new mineral is being deposited and that the newly formed mineral platelets undergo slight reshaping and reorganization during embryonic development.
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| 72. |
- Skoglund, Kristofer, 1976, et al.
(författare)
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Effect of medical treatment in patients with systemic right ventricle
- 2020
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Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:5, s. 300-305
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Congenitally corrected and surgical atrial redirected transposition of the great arteries (TGA) represents states where the morphological right ventricle serves as a systemic ventricle (S-RV). The S-RV is prone to failure, but data on medical treatment on this problem is limited. The purpose of this study was to evaluate the survival in adults with S-RV, with or without heart failure treatment.Design: The SWEDCON registry was used to collect data. All adults with S-RV and minimum follow-up of 1 year were included retrospectively. Medical treatment was defined as taking beta-blockers and/or ACE inhibitors and/or ARBs for more than 50% of the time.Results: We identified 343 patients with S-RV (median age: 21 years). Surgical atrial redirected TGA was present in 58% and congenitally corrected TGA in 42% of patients. The medically treated group (n = 126) had higher rates of impaired S-RV function, use of diuretics, pacemaker and higher NYHA functional class at baseline compared to controls. The proportion of patients with impaired functional class did not change over time in the medically treated group, but increased in controls (21% vs. 30%, p = .015). In Kaplan–Meier analysis, the mean follow-up was 10.3 years, no difference in survival was seen between the groups.Conclusions: Medical treatment may be beneficial in patients with S-RV and impaired functional class and appears to be safe in the long term. The treatment group had equal survival to controls, despite worse baseline characteristics, which might be a result of slower progression of disease in this group.
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| 73. |
- Sundh, Josefin, 1972-, et al.
(författare)
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Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
- 2020
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
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| 74. |
- Sundquist, Viktoria, 1976, et al.
(författare)
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BIM in construction production: Gains and hinders for firms, projects and industry
- 2020
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Ingår i: ARCOM 2020 - Association of Researchers in Construction Management, 36th Annual Conference 2020 - Proceedings. ; 2020, s. 505-514
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Konferensbidrag (refereegranskat)abstract
- The construction industry strives to implement digitalization and Building Information Modelling (BIM). Studies of BIM in construction claim that a pronounced BIM strategy, knowledge of the subject and a willingness to change are important factors to succeed, but even when such conditions are in place, BIM implementation in construction production is scant and has limited impact. So how should the construction industry go from grand digital visions to practical application in reality? By identifying gains, obstacles and success factors on company, project and sector levels the paper aims to set out a road map for successful BIM implementation in construction production. Data sets, both qualitative and quantitative from eleven studies of using BIM in construction production, show that although the industry is making progresses in implementing BIM and digitalization, the full potential is far from realised. Specifically, the research presents an analysis of factors in relation to (1) strategy and innovation, (2) technology, (3) organizing, and (4) ecosystem. Conclusively, all these levels are strongly interdependent and need to be considered by adopting a holistic approach to reach an enhanced implementation.
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| 75. |
- Tabatabaei, Pedram, et al.
(författare)
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Intratumoral retrograde microdialysis treatment of high-grade glioma with cisplatin
- 2020
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 162:12, s. 3043-3053
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma.Method: An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1–4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment.Results: This in vitro study showed that cisplatin could be administrated with a recovery of 41–97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2–36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment.Conclusion: This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma.
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| 76. |
- Tabatabaei, Pedram, 1978-
(författare)
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Stereotactic microdialysis for metabolic assessment and experimental treatment of malignant glioma
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma multiforme, the most common primary brain tumor, has a dire prognosis despite multimodal treatments that include surgery and radio-chemotherapy. To improve the outcome of this destructive disease, we need to improve our understanding of its tumor biology. Furthermore, the development of new treatment strategies will improve with a better understanding of the interplay between malignant cells and their direct surrounding microenvironment.This thesis aims to increase the understanding of the processes within high-grade glioma and its microenvironment during normal conditions as well as during the distress associated with treatment. Specifically, we have investigated the metabolic response to radiotherapy (study I and II), the immunologic response to radiotherapy (study II), and the metabolic response pattern to loco-regional treatment with cisplatin (study III and IV). Using microdialysis, we collected samples from the extracellular space in both normal brain and tumor tissue during radiotherapy (study I and II) and loco-regional cisplatin treatment (study III and IV). Theses samples were analyzed for glucose metabolites, glycerol, and glutamate (study I, II, and III) and for cytokines (study II). In addition, we analyzed the global metabolism with mass spectrometry to identify and assess the response pattern of malignant glioma cells to loco-regional cisplatin treatment (study IV).In study I and II, we found that malignant glioma cells used glucose at a higher rate than normal cells and preferred glycolysis for glucose metabolism. The given radiation dose (2 Gray (Gy) daily for five days) did not significantly affect glucose metabolism, glycerol levels, or glutamate levels in tumor tissue or the microenvironment. However, in study II, we observed an induced inflammatory effect due to the given radiation dose as several of the cytokines investigated showed significantly increased levels during radiotherapy. In study IV, we observed a complex and strong metabolic response to the loco-regional cisplatin therapy. At baseline, we found a metabolic pattern corresponding well with highly proliferating tumor tissue–i.e., high levels of amino acids, their metabolites, and other metabolic end products and low levels of sugar derivatives, antioxidants, and nucleotides. During the loco-regional therapy, we observed a clearly localized cytotoxic effect within the tumor and a metabolic response pattern corresponding with cisplatin’s complex mechanism of action, affecting several metabolic pathways within the malignant cell. Glutamate and glycerol also increased in tumor tissue following loco-regional treatment, a finding that further supported the observation of local toxicity.In study III, we investigated microdialysis as a method to assess the microenvironment in high-grade glioma and as a method for drug delivery (retrograde microdialysis). All studies demonstrated the usefulness of microdialysis as a tool for in vivo real-time assessment of molecular events in malignant glioma tissue. Although the method is invasive, no complications related to the surgical procedure or assessment were noted. In study III, we also demonstrated that retrograde microdialysis is a feasible method for locally delivering clinically significant doses of drugs such as cisplatin to tumor tissue in the brain. However, in addition to having a cytotoxic effect on tumor cells, cisplatin may induce clinically significant edema.
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| 77. |
- Taghavian, Hamed, 1992-, et al.
(författare)
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Fixed-order controller synthesis for monotonic closed-loop responses : A linear programming approach
- 2020
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Ingår i: IFAC-PapersOnLine. - : Elsevier BV. - 2405-8963.
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Konferensbidrag (refereegranskat)abstract
- We consider the problem of synthesizing dynamic controllers to guarantee monotonic closed-loop step responses. Restricting our attention to controllers which yield positive closed-loop systems, we derive synthesis conditions that are linear in the controller parameters. A linear programming formulation that attempts to optimize the decay rate of the closed-loop system while ensuring asymptotic stability and monotonic step response is developed. An alternative approach which guarantees closed-loop stability and a near-monotonic response is also introduced. Several illustrative examples demonstrate the effectiveness of the approach.
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| 78. |
- Thell, Arne, et al.
(författare)
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Historie, udbredelse og redningsprojekt for læge-betonie i Danmark
- 2020
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Ingår i: Urt. - 0105-3795. ; 44:2, s. 22-29
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Fra at være almindelig på Lolland i det 18. århundrede blev Læge-Betonie, (Betonica officinalis), til sidst en af de sjældneste planter i den danske flora. Dens naturlige voksepladser forsvandt, og i 2016 var der kun to blomstrende planter i helelandet, og de stod i en vejgrøft langs Bjerremarkvej i Tågerup sogn noglekilometer øst for Rødby. Vi besluttede at starte et redningsprojekt ved atsamle frøene fra de to planter og dyrke nyt materiale til plantning på stedet. Der er nu plantet hundrede eksemplarer i Bjerremark 2017–2018, hvoraf de fleste har overlevet tørken. Cirka en tredjedel af disse blomstrede i 2019.
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| 79. |
- Torsson, Emeli, et al.
(författare)
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Field-Adapted Full Genome Sequencing of Peste-Des-Petits-Ruminants Virus Using Nanopore Sequencing
- 2020
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Peste-des-petits-ruminants virus (PPRV) is currently the focus of a control and eradication program. Full genome sequencing has the opportunity to become a powerful tool in the eradication program by improving molecular epidemiology and the study of viral evolution. PPRV is prevalent in many resource-constrained areas, with long distances to laboratory facilities, which can lack the correct equipment for high-throughput sequencing. Here we present a protocol for near full or full genome sequencing of PPRV. The use of a portable miniPCR and MinION brings the laboratory to the field and in addition makes the production of a full genome possible within 24 h of sampling. The protocol has been successfully used on virus isolates from cell cultures and field isolates from tissue samples of naturally infected goats.
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| 80. |
- Van Bulck, Liesbet, et al.
(författare)
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Healthcare system inputs and patient-reported outcomes : a study in adults with congenital heart defect from 15 countries
- 2020
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The relationship between healthcare system inputs (e.g., human resources and infrastructure) and mortality has been extensively studied. However, the association between healthcare system inputs and patient-reported outcomes remains unclear. Hence, we explored the predictive value of human resources and infrastructures of the countries' healthcare system on patient-reported outcomes in adults with congenital heart disease.METHODS: This cross-sectional study included 3588 patients with congenital heart disease (median age = 31y; IQR = 16.0; 52% women; 26% simple, 49% moderate, and 25% complex defects) from 15 countries. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviors, and quality of life. The assessed inputs of the healthcare system were: (i) human resources (i.e., density of physicians and nurses, both per 1000 people) and (ii) infrastructure (i.e., density of hospital beds per 10,000 people). Univariable, multivariable, and sensitivity analyses using general linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences.RESULTS: Sensitivity analyses showed that higher density of physicians was significantly associated with better self-reported physical and mental health, less psychological distress, and better quality of life. A greater number of nurses was significantly associated with better self-reported physical health, less psychological distress, and less risky health behavior. No associations between a higher density of hospital beds and patient-reported outcomes were observed.CONCLUSIONS: This explorative study suggests that density of human resources for health, measured on country level, are associated with patient-reported outcomes in adults with congenital heart disease. More research needs to be conducted before firm conclusions about the relationships observed can be drawn.TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150603. Registered 30 May 2014.
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