| 1. |
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| 2. |
- Weinstock, Joshua S, et al.
(author)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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In: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Journal article (peer-reviewed)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, butthis effect was not seen inclones withdriver 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 experimentalknockdown 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.
(author)
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What Should We Agree on about the Repugnant Conclusion?
- 2021
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In: Utilitas. - : Cambridge University Press. - 0953-8208 .- 1741-6183. ; 33:4, s. 379-383
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
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Journal article (peer-reviewed)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.
(author)
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Echocardiography in extracorporeal life support : A key player in procedural guidance, tailoring and monitoring
- 2018
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In: Perfusion. - : Sage Publications. - 0267-6591 .- 1477-111X. ; 33:1_suppl, s. 31-41
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Journal article (peer-reviewed)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.
(author)
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Differential hypoxemia during venoarterial extracorporeal membrane oxygenation
- 2019
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In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 34:1_suppl, s. 22-29
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Journal article (peer-reviewed)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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| 10. |
- Braganca, F. M. Serra, et al.
(author)
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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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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)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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| 11. |
- Broomé, Sara, et al.
(author)
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Going Deeper than Tracking : A Survey of Computer-Vision Based Recognition of Animal Pain and Emotions
- 2023
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In: International Journal of Computer Vision. - : Springer Nature. - 0920-5691 .- 1573-1405. ; 131:2, s. 572-590
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Journal article (peer-reviewed)abstract
- Advances in animal motion tracking and pose recognition have been a game changer in the study of animal behavior. Recently, an increasing number of works go ‘deeper’ than tracking, and address automated recognition of animals’ internal states such as emotions and pain with the aim of improving animal welfare, making this a timely moment for a systematization of the field. This paper provides a comprehensive survey of computer vision-based research on recognition of pain and emotional states in animals, addressing both facial and bodily behavior analysis. We summarize the efforts that have been presented so far within this topic—classifying them across different dimensions, highlight challenges and research gaps, and provide best practice recommendations for advancing the field, and some future directions for research.
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| 12. |
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| 13. |
- Flam, B, et al.
(author)
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Authors' Response
- 2015
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In: Journal of intensive care medicine. - : SAGE Publications. - 1525-1489 .- 0885-0666. ; 52:1, s. 493-4
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Journal article (other academic/artistic)
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| 14. |
- Flam, B, et al.
(author)
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Pheochromocytoma-Induced Inverted Takotsubo-Like Cardiomyopathy Leading to Cardiogenic Shock Successfully Treated With Extracorporeal Membrane Oxygenation
- 2015
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In: Journal of intensive care medicine. - : SAGE Publications. - 1525-1489 .- 0885-0666. ; 30:6, s. 365-372
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Journal article (peer-reviewed)abstract
- Pheochromocytoma classically displays a variety of rather benign symptoms, such as headache, palpitations, and sweating, although severe cardiac manifestations have been described. We report a case of pheochromocytoma-induced inverted takotsubo-like cardiomyopathy leading to shock and cardiac arrest successfully treated with extracorporeal membrane oxygenation (ECMO) as a bridge to pharmacological therapy and curative adrenalectomy. A previously healthy 46-year-old woman presented to the emergency department with abdominal pain, dyspnea, nausea, and vomiting. Clinical evaluation revealed cardiorespiratory failure with hypoxia and severe metabolic acidosis. Computed tomography (CT) scan showed pulmonary edema and a left adrenal mass. Transthoracic echocardiography (TTE) displayed severe left ventricular dysfunction with inverted takotsubo contractile pattern. Despite mechanical ventilation and inotropic and vasopressor support, asystolic cardiac arrest ensued. The patient was resuscitated using manual chest compressions followed by venoarterial ECMO. Repeated TTEs demonstrated resolution of the cardiomyopathy within a few days. Laboratory results indicated transient renal and hepatic dysfunction, and CT scan of the brain displayed occipital infarctions. Biochemical testing and radionuclide scintigraphy confirmed a pheochromocytoma. Pharmacological adrenergic blockade was instituted prior to delayed adrenalectomy after which the diagnosis was histopathologically verified. The patient recovered after rehabilitation. We conclude that pheochromocytoma should be considered in patients presenting with unexplained cardiovascular compromise, especially if they display (inverted) takotsubo contractile pattern. Timely, adequate management might involve ECMO as a bridge to pharmacological therapy and curative surgery.
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| 15. |
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| 16. |
- Jager, R, et al.
(author)
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Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci
- 2015
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 6178-
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Journal article (peer-reviewed)abstract
- Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer–promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we develop a capture Hi-C (cHi-C) approach to allow an agnostic characterization of these physical interactions on a genome-wide scale. Single-nucleotide polymorphisms associated with complex diseases often reside within regulatory elements and exert effects through long-range regulation of gene expression. Applying this cHi-C approach to 14 colorectal cancer risk loci allows us to identify key long-range chromatin interactions in cis and trans involving these loci.
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| 18. |
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| 19. |
- Meuwese, CL, et al.
(author)
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The hemodynamic effect of different left ventricular unloading techniques during veno-arterial extracorporeal life support: a systematic review and meta-analysis
- 2020
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In: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 35:7, s. 664-671
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Journal article (peer-reviewed)abstract
- Pulmonary edema and left ventricular thrombosis may arise during veno-arterial extracorporeal life support due to an increase in cardiac load. This mechanical stress can be reduced through different left ventricular unloading techniques. We set out to quantitatively summarize the hemodynamic effects of available methods in patients treated with veno-arterial extracorporeal life support. Methods: Literature was systematically searched for studies reporting left ventricular unloading during veno-arterial extracorporeal life support as reflected by changes in left atrial pressure, pulmonary capillary wedge pressure, diastolic pulmonary artery pressure, or left ventricular end-diastolic pressure. For studies including ⩾10 patients per group, changes in these parameters were pooled using (1) standardized mean differences and (2) ratio of means. Assessment of potential bias was performed for all studies. Results: Eight studies met the inclusion criteria. Reported techniques included use of intra-aortic balloon pump (n = 1), micro-axial blood pump (Impella®, n = 2), left ventricular venting (n = 1), and atrial septostomy (n = 4). Overall, left ventricular unloading was associated with a statistically significant reduction in preload parameters (standardized mean differences = −1.05 (95% confidence interval = −1.24 to −0.86) and ratio of means = 0.60 (0.47 to 0.76)). Effect sizes were strongest for micro-axial blood pump and atrial septostomy (standardized mean differences = −1.11 (−1.55 to −0.68) and −1.22 (−1.47 to −0.96), and ratio of means = 0.58 (0.39 to 0.86) and 0.54 (0.36 to 0.83), respectively). Conclusion: Left ventricular unloading was associated with a significant reduction in left ventricular preload parameters in the setting of veno-arterial extracorporeal life support. This effect may be most pronounced for micro-axial blood pump and atrial septostomy.
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| 21. |
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| 22. |
- Åneman, A., et al.
(author)
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Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs
- 2000
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In: Critical Care Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0090-3493 .- 1530-0293. ; 28:3, s. 818-823
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.
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| 23. |
- Barkholt, L M, et al.
(author)
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Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis
- 1997
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In: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 10:6, s. 432-438
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Journal article (peer-reviewed)abstract
- Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.
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| 24. |
- Bergquist, Annika, et al.
(author)
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Perinatal events and the risk of developing primary sclerosing cholangitis
- 2006
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 12:37, s. 6037-6040
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Journal article (peer-reviewed)abstract
- AIM: To investigate whether perinatal events, intrauterine or postpartum, are associated with the development of primary sclerosing cholangitis (PSC) later in life.METHODS: Birth records from 97 patients with adult PSC in Sweden were reviewed. Information on perinatal events including medications and complications during pregnancy, gestation length, birth weight and length were collected. Two control children of the same sex were selected for each subject. Conditional multiple logistic regression was used to assess associations of the perinatal measures with development of PSC.RESULTS: No significant associations were found between gestational age, birth length, breastfeeding, and the majority of medical complications including infections or medication during pregnancy for the mothers or postpartum for the children. Vaginal bleeding and peripheral oedema showed associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and 2.28 (95% CI, 1.04-5.03), respectively. CONCLUSION: The associations of vaginal bleeding and oedema with subsequent PSC cannot readily be explained, so our findings do not strongly support the hypothesis of a significant role of perinatal events as a risk for the development of PSC later in life.
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| 25. |
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