| 1. |
- Xing, Lucas Yixi, et al.
(author)
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The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention : Results From the Randomized LOOP Study
- 2024
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In: Journal of the American Heart Association. - 2047-9980. ; 13:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. METHODS AND RESULTS: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and allcause death (hazard ratio, 1.82 [95% CI, 1.44–2.21], 2.17 [95% CI, 1.80–2.62], and 2.19 [95% CI, 1.87–2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction >0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable. CONCLUSIONS: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study.
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| 2. |
- Bodin, Maja, et al.
(author)
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Preconditions to parenthood : changes over time and generations
- 2021
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In: Reproductive Biomedicine & Society Online. - : Elsevier. - 2405-6618. ; 13, s. 14-23
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Journal article (peer-reviewed)abstract
- Reproductive decision-making and fertility patterns change with time and place, and are influenced by contemporary societal factors. In this paper, we have studied biosocial aspects of reproductive decision-making over time and generations in a Nordic setting. The aim was to explore intergenerational changes and influences on decision-making, especially regarding preconditions to first birth. Twenty-six focus group interviews were conducted in southern Sweden, including a total of 110 participants aged 17–90 years. The analysis of the interviews resulted in six themes: (i) ‘Providing security – an intergenerational precondition’; (ii) ‘A growing smorgasbord of choices and requirements’; (iii) ‘Parenthood becoming a project’; (iv) ‘Stretched out life stages’; (v) ‘(Im)possibilities to procreate’; and (vi) ‘Intergenerational pronatalism’. Our findings reflect increasing expectations on what it means to be prepared for parenthood. Despite increasing awareness of the precariousness of romantic relationships, people still wish to build new families but try to be as prepared as possible for adverse events. The findings also show how increasing life expectancy and medical advancements have come to influence people’s views on their reproductive timeline.
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| 3. |
- Borthwick, Verity, 1983-, et al.
(author)
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In-situ 3DXRD annealing of a geological material : Evaluating the validity of 2D
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Other publication (other academic/artistic)abstract
- Most in-situ heating experiments where substructure is investigated have been restricted to 2D. We compare a 2D experiment to a 3D X-ray diffraction experiment to evaluate the validity of the 2D method. Until now 3D X-ray diffraction has been limited to well-recovered substructures. We conducted a 3D in-situ annealing experiment on a halite crystal with a significant orientation gradient. This is the first experiment of its kind on a geological material and shows that even complicated microstructures can be resolved. Comparison of 2D and 3D showed that, although general results were similar, subgrain boundary movement occurred with higher frequency in 3D. We suggest this discrepancy is due to enhanced drag force on subgrain boundaries by surface thermal grooving. Thus, while results from 2D experiments largely reflect what is happening in the volume, analysis of boundary movement with regard to absolute mobilities needs to be considered with some care.
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| 4. |
- Borthwick, Verity, 1983-, et al.
(author)
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Substructure dynamics in halite : Comparison of 2D in-situ annealing experiments with 3D X-ray diffraction annealing
- 2009
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In: Deformation Mechanisms, Rheology and Tectonics 2009.
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Conference paper (other academic/artistic)abstract
- The understanding of substructural behaviour during post-deformational annealing is key to interpreting rheological adjustments during tectonic change, and the processes which cause them. The focus of this study is to use in-situ experimental techniques to increase understanding of substructure dynamics in geological materials. 2D in-situ annealing experiments have been conducted in the scanning electron microscope, using electron backscatter diffraction (EBSD) to collect information about the crystallographic orientation of the surface. A single crystal of halite, pre-deformed under uniaxial compression at temperatures of ~450 ºC with a strain rate of 6.9x10-6s-1, and to a final strain of 0.165, was examined. Different temperature time-paths were investigated with temperatures between 280-470 ºC and durations of heating between 30 min and 6 h. EBSD maps were taken before, during and after heating. Behaviour during annealing was found to be temperature dependent and could be divided into three main phases of development. Subgrain boundaries could be divided into five categories based on behaviour during annealing, morphology and orientation. Annealing behaviour could be directly related to preferential activation of one set of slip systems due to the chosen aspect ratio of the crystal. While the 2D experiments provided valuable information, it is impossible to rule out the potential influence surface effects may have on annealing behaviour. In order to verify the results of these experiments, a 3D X-ray diffraction experiment was conducted at the synchrotron in Grenoble, France. The experiment followed a similar heating procedure as that for the 2D experiments and was performed on the same sample. This newly developed technique allows non-destructive internal examination of the crystal. Data was collected before, during and after each heating stage. During heating crystallographic information was collected within a limited rotation threshold (12-30º) in order to illuminate one or two subgrains and allow us to follow their progress. Comparison of the shape and strength of intensity spots has allowed us to draw some early conclusions from the data without a full crystallographic analysis. Preliminary results suggest that similar processes may be occurring as those observed in the 2D experiments, including spots becoming more distinct as well as some spots rotating away from the bulk of the subgrain indicating some subdivision and potential polygonisation. We can thus suggest that some of the behaviour exhibited in the 3D experiment is similar to that from the 2D experiment. Full crystallographic analysis of large maps taken after heating will allow us to examine the behaviour of the substructure in more detail and potentially rule out surface effects from the 2D experiments.
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| 5. |
- Borthwick, Verity, et al.
(author)
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The application of in-situ 3D X-ray Diffraction in annealing experiments : First interpretation of substructure development in deformed NaCl
- 2010
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In: Recrystallization and Grain Growth.
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Conference paper (peer-reviewed)abstract
- In-situ 3D X-ray diffraction (3DXRD) annealing experiments were conducted at the ID-11 beamline at the European Synchrotron Radiation Facility in Grenoble. This allowed us to non-destructively document and subsequently analyse the development of substructures during heating, without the influence of surface effects. A sample of deformed single crystal halite was heated to between 260-400 ºC. Before and after heating a volume of 500 by 500 by 300 mm was mapped using a planar beam, which was translated over the sample volume at intervals of 5-10 µm in the vertical dimension. In the following we present partially reconstructed orientation maps over one layer before and after heating for 240min at 260 ºC. Additional small syn-heating “maps” over a constrained sample rotation of 12-30º. The purpose of this was to illuminate a few reflections from 1 or 2 subgrains and follow their evolution during heating. Preliminary results show that significant changes occurred within the sample volume, for which, surface effects can be excluded. Results show a number of processes, including: i) change in subgrain boundary misorientation angle and ii) subgrain subdivision into areas of similar lattice orientation with new subgrain boundary formation. These results demonstrate that 3DXRD coupled with in-situ heating is a successful non-destructive technique for examining real-time post-deformational annealing in strongly deformed crystalline materials with complicated microstructures.
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| 6. |
- Carstensen, Andreas, et al.
(author)
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The Impacts of Phosphorus Deficiency on the Photosynthetic Electron Transport Chain.
- 2018
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In: Plant physiology. - : Oxford University Press (OUP). - 1532-2548 .- 0032-0889. ; 177:1, s. 271-284
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Journal article (peer-reviewed)abstract
- Phosphorus (P) is an essential macronutrient, and P deficiency limits plant productivity. Recent work showed that P deficiency affects electron transport to photosystem I (PSI), but the underlying mechanisms are unknown. Here, we present a comprehensive biological model describing how P deficiency disrupts the photosynthetic machinery and the electron transport chain through a series of sequential events in barley (Hordeum vulgare). P deficiency reduces the orthophosphate concentration in the chloroplast stroma to levels that inhibit ATP synthase activity. Consequently, protons accumulate in the thylakoids and cause lumen acidification, which inhibits linear electron flow. Limited plastoquinol oxidation retards electron transport to the cytochrome b6f complex, yet the electron transfer rate of PSI is increased under steady-state growth light and is limited under high-light conditions. Under P deficiency, the enhanced electron flow through PSI increases the levels of NADPH, whereas ATP production remains restricted and, hence, reduces CO2 fixation. In parallel, lumen acidification activates the energy-dependent quenching component of the nonphotochemical quenching mechanism and prevents the overexcitation of photosystem II and damage to the leaf tissue. Consequently, plants can be severely affected by P deficiency for weeks without displaying any visual leaf symptoms. All of the processes in the photosynthetic machinery influenced by P deficiency appear to be fully reversible and can be restored in less than 60 min after resupply of orthophosphate to the leaf tissue.
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| 7. |
- Castell, Alina, et al.
(author)
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MYCMI-7 : A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner
- 2022
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In: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 2:3, s. 182-201
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Journal article (peer-reviewed)abstract
- Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered "undruggable," and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these molecules, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC, and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN-dependent manner and downregulates the MYC pathway on a global level as determined by RNA sequencing. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy toward a collection of patient-derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells be- come G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer, and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregu- lates MYC/MYCN, inhibits tumor growth, and prolongs survival through apoptosis with few side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for the treatment of MYC-driven cancer.Significance: Our findings demonstrate that the small-molecule MYCMI-7 binds MYC and inhibits interaction between MYC and MAX, thereby ham- pering MYC-driven tumor cell growth in culture and in vivo while sparing normal cells.
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| 8. |
- Cereser, Alberto, et al.
(author)
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Time-of-Flight Three Dimensional Neutron Diffraction in Transmission Mode for Mapping Crystal Grain Structures
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Journal article (peer-reviewed)abstract
- The physical properties of polycrystalline materials depend on their microstructure, which is the nano- to centimeter scale arrangement of phases and defects in their interior. Such microstructure depends on the shape, crystallographic phase and orientation, and interfacing of the grains constituting the material. This article presents a new non-destructive 3D technique to study centimeter-sized bulk samples with a spatial resolution of hundred micrometers: time-of-flight three-dimensional neutron diffraction (ToF 3DND). Compared to existing analogous X-ray diffraction techniques, ToF 3DND enables studies of samples that can be both larger in size and made of heavier elements. Moreover, ToF 3DND facilitates the use of complicated sample environments. The basic ToF 3DND setup, utilizing an imaging detector with high spatial and temporal resolution, can easily be implemented at a time-of-flight neutron beamline. The technique was developed and tested with data collected at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Complex (J-PARC) for an iron sample. We successfully reconstructed the shape of 108 grains and developed an indexing procedure. The reconstruction algorithms have been validated by reconstructing two stacked Co-Ni-Ga single crystals, and by comparison with a grain map obtained by post-mortem electron backscatter diffraction (EBSD).
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| 9. |
- Girlanda, Orlando, et al.
(author)
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Characterization and Modelling of the Mechanical Properties of Pressboard
- 2013
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In: 2013 IEEE Conference on Electrical Insulation and Dielectric Phenomena (CEIDP). - : IEEE. - 9781479925964 ; , s. 563-566
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Conference paper (peer-reviewed)abstract
- Cellulose-based components constitute the bulk of the current insulation for transformers. Cellulose is an organic polymer material which combines excellent electrical properties and good mechanical performance. As a polymeric material, cellulose is very sensitive to moisture and temperature. These factors can influence the electrical and mechanical performance of a transformer throughout its lifetime. In order to ensure the quality of the product during transformer manufacturing, as well as during transformer life-time services, adequate models for predicting the physical properties of its constituents are needed. The present investigation tackles the mechanical description of pressboard. For this purpose, a three dimensional mechanical model is developed for simulating the in-plane and out-of-plane behavior of the pressboard material. The model is based on an anisotropic viscoelastic-viscoplastic constitutive law, which includes features that are particular for cellulose-based materials, e.g. the peculiar double nature of fiber-network-based and porous material. The material is orthotropic by nature, i.e. the in-plane mechanical properties markedly differ from the out-of-plane ones. Particular regard is taken when considering the effect of out-of-plane stresses which both cause viscous deformation and permanent compaction. The analyses on the mechanical behavior of pressboard are performed by comparing the experimental data on pressboard and the results of model simulations.
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| 10. |
- Girlanda, Orlando, et al.
(author)
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Modeling and experimental validation of the mechanical behavior of pressboard
- 2014
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In: Proceedings of the 2014 Electrical Insulation Conference. - : IEEE conference proceedings. ; , s. 203-207
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Conference paper (peer-reviewed)abstract
- High density (HD) pressboard is an essential element in power transformers combining good electrical insulation properties with effective mechanical characteristics that well suit design requirements of power transformers. In order to ensure a correctly functioning transformer, it is therefore very important to characterize and to understand the mechanical properties of pressboard under different operating conditions. Pressboard is composed of natural polymeric chains, whose mechanical properties are affected by moisture and temperature. Moreover, temperature and moisture conditions in power transformers vary throughout manufacturing process and service/operation life-time. An accurate definition of the mechanical properties is, therefore, necessary.The present article focuses on the effect of different combinations of temperature/moisture and mechanical load on the deformation behavior of HD pressboard samples. A mechanical constitutive model is developed for finite element (FEM) simulation based on a viscoelastic–viscoplastic material description. Special attention is given on the complex through-thickness deformation behavior of HD pressboard. Thorough analyses are performed based on the comparisons between the results of experimental characterization and FEM modeling and simulations. The good agreement between experimental and modeling results shows a great potential for application in mechanical design of transformer insulation.
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