| 3011. |
- Teerlink, John R., et al.
(author)
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Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials
- 2020
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:11, s. 2160-2171
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Journal article (peer-reviewed)abstract
- Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class >= II, ejection fraction <= 35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m(2) (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
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| 3012. |
- ter Steege, Hans, et al.
(author)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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In: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Journal article (peer-reviewed)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 3013. |
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| 3014. |
- Tetui, Moses, et al.
(author)
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Role satisfaction among community volunteers working in mass COVID-19 vaccination clinics, Waterloo Region, Canada
- 2023
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In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Journal article (peer-reviewed)abstract
- Introduction: Unpaid community volunteers are a vital public health resource in times of crisis. In response to the COVID-19 pandemic, community volunteers were mobilized to support mass vaccination efforts in many countries. To have this group’s continued engagement, it is essential to understand the community volunteer experience, including the opportunities and challenges they encounter and how these contribute to their role satisfaction. This qualitative study investigated the factors contributing to community volunteers’ role satisfaction at COVID-19 mass vaccination clinics in the Region of Waterloo, Canada.Methods: Qualitative data were analyzed from 20 volunteers (aged 48–79 years) who had worked at one of four COVID-19 vaccination clinics in the Region of Waterloo, Canada. Data were analyzed thematically using an inductive coding process followed by an iterative process of grouping and identifying linkages and relationships within the themes.Results: Four interrelated themes were developed from the inductive analysis process. The theme of community volunteers feeling valued or disesteemed in their role depends on the interaction between the three themes of role description, role preparation, and clinic context.Conclusions: For volunteers in crises such as the COVID-19 pandemic, volunteer role satisfaction depends on how their contributions are valued, the clarity of their role descriptions, volunteer-specific training, and the sentiments of volunteers and staff within the clinic context. Greater role satisfaction can help with retention as volunteers become more resilient and adaptable to the complex dynamic circumstances of a crisis response. Activities such as training and materials development for role preparations should be explicitly planned and well-resourced, even in crisis/pandemic situations. Building clinic managers’ or supervisors’ skills in communication during crisis/pandemic situations and the skills for the creation of team cohesion are critical investment areas.
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| 3015. |
- Teuscher, Alina C., et al.
(author)
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Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics. Longevity interventions slow age-related collagen stiffening and prolong the expression of collagens that are turned over. These prolonged collagen dynamics are mediated by a mechanical feedback loop of hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression and longevity via the transcriptional co-activator YAP-1 across tissues. Our results provide in-vivo evidence that coordinated ECM remodeling through mechanotransduction is required and sufficient to promote longevity, offering potential avenues for interventions targeting ECM dynamics.
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| 3016. |
- Thanh, Tran Dang, et al.
(author)
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Magnetic properties and magnetocaloric effect in Fe90-xNixZr10 alloy ribbons
- 2013
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 113:21, s. 213908-
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Journal article (peer-reviewed)abstract
- We report magnetic properties and magnetocaloric (MC) effect in Fe90-xNixZr10 (x = 0, 5, 10, and 15) alloy ribbons prepared by rapid-quenching method. We found the Curie temperature (T-C) of the alloy ribbons depends strongly on Ni-doping concentration (x) increasing from 245 K for (x = 0), through 306 K (for x = 5) up to T-C = 403 (for x = 15). Also, the dependence of the maximum magnetic entropy change (vertical bar Delta S-max vertical bar) on Ni content was readily apparent. Indeed, for the x = 0 and 5 samples that have T-C around room temperature, the vertical bar Delta S-max vertical bar values increment under magnetic field changes of 10, 20, and 40 kOe was found to be as high as 0.87, 1.76, and 3.04 J.kg(-1).K-1 for x = 0, and 1.03, 1.90, and 3.26 J.kg(-1).K-1 for x = 5, respectively. These values correspond to refrigerant capacity in the range of 86-334 J.kg(-1) and are comparable to other known MC materials. High magnetocaloric performance in rare-earth-free non-expensive metallic alloys indicates that these materials could be competitive candidate for active magnetic refrigeration at room temperature.
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| 3017. |
- Theißen, S., et al.
(author)
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Concept for combining LCA and hazardous building material assessment for decision support using BIM
- 2022
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In: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 1078:1
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Conference paper (peer-reviewed)abstract
- The construction and building sector is responsible for a large part of the world's resource and energy consumption and is considered the largest global emitter of greenhouse gas (GHG) emissions. Hazardous and toxic substances in building materials affect indoor air quality as well as the environment and thus have a high impact on human health, as we spend around 90 percent of our lives in buildings. Life cycle assessment (LCA) and hazardous building material requirements of green building certification systems allow to reduce the environmental and health impacts of building products and materials. However, they are usually very complex and time-consuming to perform and require expert knowledge to use the results for decision support. Digital approaches to support the simplified application of these methods and intuitive visualization of results are becoming increasingly important. Especially Building Information Modeling (BIM) offers a high potential for this purpose, as the integration and linking of geometric and semantic information in 3D-models for LCA and hazardous building material assessment can be done much more efficiently and intuitively. Within the scope of this work, the following three objectives were pursued (1) development of a method for combining LCA and hazardous building material assessment, (2) simplification of the results by converting them into comprehensible indicators for decision support, and (3) implementation of the method in a BIM-based digital assistant for intuitive visualization and communication. The preliminary results show a concept for combined use of LCA and hazardous building material assessment in Germany with differentiation in six use cases. A prototypical implementation as BIM-integrated digital assistant was developed for one of these use cases. For the first time, this prototype provides understandable feedback in real time of LCA and hazardous building material requirements. This research project contributes to the awareness in the context of embodied impacts and low emitting materials in buildings and advances the current digitalization potentials.
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| 3018. |
- Thielemann-Kühn, Nele, et al.
(author)
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Optical control of 4f orbital state in rare-earth metals
- 2024
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:16
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Journal article (peer-reviewed)abstract
- A change of orbital state alters the coupling between ions and their surroundings drastically. Orbital excitations are hence key to understand and control interaction of ions. Rare-earth elements with strong magneto-crystalline anisotropy (MCA) are important ingredients for magnetic devices. Thus, control of their localized 4f magnetic moments and anisotropy is one major challenge in ultrafast spin physics. With time-resolved x-ray absorption and resonant inelastic scattering experiments, we show for Tb metal that 4f-electronic excitations out of the ground-state multiplet occur after optical pumping. These excitations are driven by inelastic 5d-4f-electron scattering, altering the 4f-orbital state and consequently the MCA with important implications for magnetization dynamics in 4f-metals and more general for the excitation of localized electronic states in correlated materials.
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| 3019. |
- Thiemann, Ellen, et al.
(author)
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Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling
- 2022
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In: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
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Journal article (peer-reviewed)abstract
- Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis. By metabolic studies we found that cold-induced triglyceride uptake into BAT, lipoprotein disposal, glucose uptake and adaptive thermogenesis were not impaired in mice lacking Lpl exclusively in endothelial cells. This finding may be explained by a compensatory upregulation in the expression of adipocyte-derived Lpl and endothelial lipase (Lipg).
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| 3020. |
- Thiselton, DL, et al.
(author)
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A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy
- 2002
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In: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 43:6, s. 1715-1724
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Journal article (peer-reviewed)abstract
- PURPOSE. To characterize the spectrum of mutations in the OPA1 gene in a large international panel of patients with autosomal dominant optic atrophy (adOA), to improve understanding of the range of functional deficits attributable to sequence variants in this gene, and to assess any genotype-phenotype correlations. METHODS. All 28 coding exons of OPA1, intron-exon splice sites, 273 bp 5' to exon 1, and two intronic regions with putative function were screened in 94 apparently unrelated white patients of European origin with adOA by single-strand conformational polymorphism (SSCP)-heteroduplex analysis and direct sequencing. Clinical data were collated, and putative mutations were tested for segregation in the respective families by SSCP analysis or direct sequencing and in 100 control chromosomes. Further characterization of selected splice site mutations was performed by RT-PCR of patient leukocyte RNA. Staining of mitochondria in leukocytes of patients and control subjects was undertaken to assess gross differences in morphology and cellular distribution. RESULTS. Twenty different mutations were detected, of which 14 were novel disease mutations (missense, nonsense, deletion-frameshift, and splice site alterations) and six were known mutations. Mutations were found in 44 (47%) of the 94 families, included in the study. Ten new polymorphisms in the OPA1 gene were also identified. Mutations occur throughout the gene, with three clusters emerging: in the mitochondrial leader, in the highly conserved guanosine triphosphate (GTP)-binding domain, and in the -COOH terminus. Examination of leukocyte mitochondria from two unrelated patients with splice site mutations in OPA1 revealed no abnormalities of morphology or cellular distribution when compared with control individuals. CONCLUSIONS. This study describes 14 novel mutations in the OPA1 gene in patients with adOA, bringing the total number so far reported to 54. It is likely that many cases of adOA are due to mutations outside the coding region of OPA1 or to large-scale rearrangements. Evaluation of the mutation spectrum indicates more than one pathophysiological mechanism for adOA. Preliminary data suggests that phenotype-genotype correlation is complex, implying a role for other genetic modifying or environmental factors. No evidence was found of pathologic changes in leukocyte mitochondria of patients with adOA.
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