| 1. |
- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 2. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 3. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 4. |
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| 5. |
- Bagni, Tommaso, et al.
(författare)
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Modeling Results of the Quench Behavior of a Nb-Ti Canted-Cosine-Theta Corrector Magnet for LHC
- 2024
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Ingår i: IEEE transactions on applied superconductivity (Print). - : Institute of Electrical and Electronics Engineers (IEEE). - 1051-8223 .- 1558-2515. ; 34:5, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- A newly designed superconducting magnet of the Canted-Cosine-Theta (CCT) type was developed as a result of a collaboration between Swedish universities (Uppsala and Linneaus) and Swedish industries. This magnet was designed to function as a replacement of the present LHC orbit corrector magnets, which are approaching their end of life due to the radiation load. As a result, the new CCT magnet was developed to be more radiation tolerant and to constitute a one-to-one replacement to the currently installed version, which is a 1 m long 70 mm double aperture dipole magnet. The final magnet, which is currently under construction, will be tested at FREIA laboratory at Uppsala University and generate a magnetic field of 3.3 T and an integrated field of 2.8 Tm at about 85 A. To examine the magnet quench behavior and to identify a suitable quench protection system, the 3D electro-magnetic and thermal behavior of the coil was modeled using the RAT-Raccoon software. Based on the simulation results, a Metrosil varistor was selected to protect the magnet during the test. In this article, we report the results of the numerical analysis. The magnet model is equipped with a spot heater to initialize the quench and the temperature and voltages are monitored during the avalanche effect. The simulated current decay and the hot-spot temperature are analyzed with a focus on the impact of quench-back on the magnet protection.
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| 6. |
- Paulsson, Magnus, et al.
(författare)
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Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of Pseudomonas aeruginosa bacteraemia : a retrospective cohort study
- 2017
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 36:7, s. 1187-1196
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Tidskriftsartikel (refereegranskat)abstract
- Ineffective antimicrobial therapy of Pseudomonas aeruginosa bacteraemia increases mortality. Recent studies have proposed the use of antimicrobial combination therapy composed of a beta-lactam with either ciprofloxacin or tobramycin. To determine if combination therapy correlates to lower mortality and is superior compared to monotherapy, we investigated the effect of antimicrobial treatment regimens on 30-day mortality in a cohort with Pseudomonas aeruginosa bacteraemia. All cases of P. aeruginosa bacteraemia (n = 292) in southwest Skåne County, Sweden (years 2005–2010, adult population 361,112) and the whole county (2011–2012, 966,130) were identified. Available medical and microbiological records for persons aged 18 years or more were reviewed (n = 235). Antimicrobial therapy was defined as empiric at admission or definitive after culture results and was correlated to 30-day mortality in a multivariate regression model. The incidence and mortality rates were 8.0 per 100,000 adults and 22.9% (67/292), respectively. As expected, multiple comorbidities and high age were associated with mortality. Adequate empiric or definitive antipseudomonal treatment was associated with lower mortality than other antimicrobial alternatives (empiric p = 0.02, adj. p = 0.03; definitive p < 0.001, adj. p = 0.007). No difference in mortality was seen between empiric antipseudomonal monotherapy or empiric combination therapy. However, definitive combination therapy including ciprofloxacin correlated to lower mortality than monotherapy (p = 0.006, adj. p = 0.003), whereas combinations including tobramycin did not. Our results underline the importance of adequate antipseudomonal treatment. These data also suggest that P. aeruginosa bacteraemia should be treated with an antimicrobial combination including ciprofloxacin when susceptible.
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| 7. |
- Pepitone, Kevin, Dr, 1988-, et al.
(författare)
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Design and Fabrication of a Canted-Cosine-Theta Double Aperture Orbit Corrector Dipole for the LHC
- 2023
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Ingår i: IEEE transactions on applied superconductivity (Print). - : IEEE. - 1051-8223 .- 1558-2515. ; 33:5
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Tidskriftsartikel (refereegranskat)abstract
- A prototype CCT dipole magnet developed by a collaboration between Swedish universities, Swedish industry and CERN will be tested at Uppsala University. This 1 m long double-aperture magnet can provide a field strength of 3.3 T at 85 A in a 70 mm aperture with an integrated field of 2.8 Tm. It is intended to replace the current LHC orbit corrector magnets which are reaching the end of their expected life due to the radiation load. The new magnet is designed to handle the radiation dose of the upgrade to the high-luminosity LHC, which will deliver about ten times the current radiation dose. It must therefore be more resistant to radiation and meet strict requirements in terms of electrical insulation while matching the original field quality and self-protective capability, mechanical volume, and maximum excitation current. This paper will present the latest of the design and manufacturing work, including the results of simulations of the mechanical field and the mechanical stress. Details of the various tests performed before machining the parts are also presented.
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| 8. |
- Ahl, Helene J.
(författare)
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The Making of the Female Entrepreneur : A Discourse Analysis of Research Texts on Women’s Entrepreneurship
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Departing from a social constructionist understanding of gender, this thesis examines how the female entrepreneur is constructed in research articles about women’s entrepreneurship. It finds that even if the texts celebrate women’s entrepreneurship, they do it in such a way as to recreate women’s secondary position in society.Building on Foucault’s theory of discourse, the thesis analyzes the discursive practices by which this result was achieved. These practices include certain assumptions that are taken for granted about women, men, business, work, and family. One of these assumptions is that men and women must be different. Despite research results to the contrary, many texts insist that the genders are different and construct three kinds of arguments in support of this. One is making a mountain out of a molehill, i.e. stressing small differences while ignoring similarities. Another is the self-selected woman, which proclaims women entrepreneurs as unusual women. The third is called the good mother and consists of molding an alternative, feminine model of entrepreneurship while leaving the dominant model intact. These arguments reproduce the idea of essential gender differences and the idea of the woman as the weaker sex.The discursive practices also include certain ontological and epistemological assumptions, which are questioned in the thesis. In addition, they contain disciplinary regulations as well as writing and publishing practices that reinforce the discourse. The practices and the ensuing research results are moreover dependent on the particular context in which the articles are produced. This means that their results and conclusions cannot be transferred to other contexts uncritically.By discussing these practices, the thesis opens the way for alternative ways of theorizing and researching women’s entrepreneurship. Suggestions for alternative research practices include the addition of institutional aspects to the research agenda, such as labor market structure, family policy, and legislation. The thesis also suggests a shift in epistemological position – from gender as something that is given, to gender as something that is produced.
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| 9. |
- Ahl, Ing-Marie, 1974-, et al.
(författare)
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Coexpression of yeast copper chaperone (yCCS) and CuZn-superoxide dismutases in Escherichia coli yields protein with high copper contents
- 2004
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928 .- 1096-0279. ; 37:2, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- To fully understand the function of the Cu- and Zn-containing superoxide dismutases in normal and disordered cells, it is essential to study protein variants with full metal contents. We describe the use of an Escherichia coli-based expression system for the overproduction of human intracellular wild type CuZn-superoxide dismutase (SOD), the CuZnSOD variant F50E/G51E (monomeric), two amyotrophic lateral sclerosis-related mutant CuZnSOD variants (D90A and G93A), and PseudoEC-SOD, all with high Cu contents. This system is based on coexpression of the SOD variants with the yeast copper chaperone yCCS during growth in a medium supplemented with Cu2+ and Zn2+. The recombinant SOD enzymes were all found in the cytosol and represented 30-50% of the total bacterial protein. The enzymes were purified to homogeneity and active enzymes were obtained in high yield. The resulting proteins were characterized through immunochemical reactivity and specific activity analyses, in conjunction with mass-, photo-, and atomic absorption-spectroscopy. © 2004 Elsevier Inc. All rights reserved.
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| 10. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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Does beta-blockade reduce the risk of depression in patients with isolated severe extracranial injuries?
- 2017
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Ingår i: World Journal of Surgery. - New York : Springer. - 0364-2313 .- 1432-2323. ; 41:7, s. 1801-1806
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury.METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011. Severe extracranial injuries were defined as extracranial injuries with Abbreviated Injury Scale score ≥3, intracranial Abbreviated Injury Scale score <3 and an Injury Severity Score ≥16. In-hospital deaths and patients prescribed antidepressant therapy ≤1 year prior to admission were excluded. Patients were stratified into groups based on pre-admission beta-blocker status. The primary outcome was post-traumatic depression, defined as receiving antidepressants ≤1 year following trauma.RESULTS: Five hundred and ninety-six patients met the inclusion criteria with 11.4% prescribed pre-admission beta-blockade. Patients receiving beta-blockers were significantly older (57 ± 18 vs. 42 ± 17 years, p < 0.001) with lower Glasgow Coma Scale score (12 ± 3 vs. 14 ± 2, p < 0.001). The beta-blocked cohort spent significantly longer in hospital (21 ± 20 vs. 15 ± 17 days, p < 0.01) and intensive care (4 ± 7 vs. 3 ± 5 days, p = 0.01). A forward logistic regression model was applied and predicted lack of beta-blockade to be associated with increased risk of depression (OR 2.7, 95% CI 1.1-7.2, p = 0.04). After adjusting for group differences, patients lacking beta-blockers demonstrated an increased risk of depression (AOR 3.3, 95% CI 1.2-8.6, p = 0.02).CONCLUSIONS: Pre-admission beta-blockade is associated with a significantly reduced risk of depression following severe traumatic injury. Further investigation is needed to determine the beneficial effects of beta-blockade in these instances.
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