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| 2. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, but this effect was not seen in clones with driver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimental knockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 3. |
- Zuber, S., et al.
(författare)
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What Should We Agree on about the Repugnant Conclusion?
- 2021
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Ingår i: Utilitas. - : Cambridge University Press. - 0953-8208 .- 1741-6183. ; 33:4, s. 379-383
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Tidskriftsartikel (refereegranskat)abstract
- The Repugnant Conclusion is an implication of some approaches to population ethics. It states, in Derek Parfit's original formulation, For any possible population of at least ten billion people, all with a very high quality of life, there must be some much larger imaginable population whose existence, if other things are equal, would be better, even though its members have lives that are barely worth living. (Parfit 1984: 388) Copyright © The Author(s), 2021. Published by Cambridge University Press.
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| 4. |
- Steding-Ehrenborg, K, et al.
(författare)
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Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF
- 2021
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
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Tidskriftsartikel (refereegranskat)abstract
- It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.
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| 5. |
- Donker, D. W., et al.
(författare)
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Echocardiography in extracorporeal life support : A key player in procedural guidance, tailoring and monitoring
- 2018
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Ingår i: Perfusion. - : Sage Publications. - 0267-6591 .- 1477-111X. ; 33:1_suppl, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.
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| 6. |
- Falk, L, et al.
(författare)
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Differential hypoxemia during venoarterial extracorporeal membrane oxygenation
- 2019
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Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 34:1_suppl, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- Venoarterial extracorporeal membrane oxygenation, indicated for severe cardio-respiratory failure, may result in anatomic regional differences in oxygen saturation. This depends on cannulation, hemodynamic state, and severity of respiratory failure. Differential hypoxemia, often discrete, may cause clinical problems in peripheral femoro-femoral venoarterial extracorporeal membrane oxygenation, when the upper body is perfused with low saturated blood from the heart and the lower body with well-oxygenated extracorporeal membrane oxygenation blood. The key is to diagnose and manage fulminant differential hypoxemia, that is, a state that may develop where the upper body is deprived of oxygen. We summarize physiology, assessment of diagnosis, and management of fulminant differential hypoxemia during venoarterial extracorporeal membrane oxygenation. A possible solution is implantation of an additional jugular venous return cannula. In this article, we propose an even better solution, to drain the venous blood from the superior vena cava. Drainage from the superior vena cava provides superiority to venovenoarterial configuration in terms of physiological rationale, efficiency, safety, and simplicity in clinical circuit design.
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| 8. |
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| 9. |
- Larsson, M, et al.
(författare)
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When Life-Saving Is Life-Threatening
- 2014
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Ingår i: SCIENCE TRANSLATIONAL MEDICINE. - 1946-6234. ; 6:222
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Braganca, F. M. Serra, et al.
(författare)
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Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.
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