| 1. |
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Overview of the JET results
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Esteve-Codina, Anna, et al.
(författare)
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Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.
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| 3. |
- Schilling, Thomas, 1966-, et al.
(författare)
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Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation
- 2007
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 99:3, s. 368-375
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) induces a pro-inflammatory response including cytokine release and leucocyte recruitment in the ventilated lung. Whether volatile or i.v. anaesthetics differentially modulate the alveolar inflammatory response to OLV is unclear. METHODS: Thirty patients, ASA II or III, undergoing open thoracic surgery were randomized to receive either propofol 4 mg kg(-1) h(-1) (n = 15) or 1 MAC desflurane in air (n = 15) during thoracic surgery. Analgesia was provided by i.v. infusion of remifentanil (0.25 microg kg(-1) min(-1)) in both groups. The patients were mechanically ventilated according to a standard protocol during two-lung ventilation and OLV. Fibre optic bronchoalveolar lavage (BAL) of the ventilated lung was performed before and after OLV and 2 h postoperatively. Alveolar cells, protein, tumour necrosis factor alpha (TNFalpha), interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN) elastase were determined in the BAL fluid. Data were analysed by parametric or non-parametric tests, as indicated. RESULTS: In both groups, an increase in pro-inflammatory markers was found after OLV and 2 h postoperatively; however, the fraction of alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05) was significantly higher in the propofol group compared with the desflurane group. The time courses of alveolar elastase, IL-8, and IL-10 differed between groups, and alveolar TNFalpha (7.4 vs 3.1 pg ml(-1), P < 0.05) and sICAM-1 (52.3 vs 26.3 ng ml(-1), P < 0.05) were significantly higher in the propofol group. CONCLUSIONS: These data indicate that pro-inflammatory reactions during OLV were influenced by the type of general anaesthesia. Different patterns of alveolar cytokines may be a result of increased granulocyte recruitment during propofol anaesthesia.
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| 4. |
- Schilling, Thomas, et al.
(författare)
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The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery
- 2005
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Ingår i: Anesthesia and Analgesia. - : International Anesthesia Research Society. - 0003-2999 .- 1526-7598. ; 101:4, s. 957-965
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. IMPLICATIONS: Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.
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| 5. |
- Schuette, Moritz, et al.
(författare)
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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| 6. |
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| 7. |
- Bottke, Dirk, et al.
(författare)
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Adjuvant radiotherapy after radical prostatectomy
- 2007
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Ingår i: European Journal of Cancer Supplements. - 1359-6349. ; 5:5, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate-specific antigen (PSA) as a sign of local and/or systemic tumour progression. Adjuvant radiotherapy (RT) for positive margins (RI) aims to reduce residual tumour cells in the prostatic bed, thus possibly reducing the biochemical progression rate. Apart from a large number of retrospective investigations, available results are presented from three randomised studies which have either been published completely (or in abstract form). Results: For pT3 prostate carcinomas, agreeing data are presented from three randomised studies, which show around a 20% reduced biochemical progression rate (bNED) after 4 to 5 years. With these data the results of numerous retrospective studies were confirmed. The majority of the authors used total doses of 60 Gy. From one randomised study an increased local control rate was demonstrated as basis for the extended freedom of biochemical progression. The rate of acute and late side effects after three-dimensional (3-D) planned radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data situation for pT2 prostate carcinomas with positive margins is worse. Here, controversial data are presented, which require further investigation. Only retrospective data demonstrated a 25% advantage for adjuvant RT. Therefore, adjuvant radiotherapy also seems reasonable for pT-2 carcinomas with positive margins. Conclusions: The effectiveness of adjuvant radiotherapy for patients with pT-3 tumours with positive margins with and without undetectable PSA levels with 60 Gy total dose has been demonstrated. A survival advantage has not been shown until now. 3-D treatment planning remains the standard technique for these patients. For patients with positive margins in organ-limited prostate carcinomas (pT2 R 1) randomised studies are recommended. It remains unclear whether the adjuvant RT is superior to the radiotherapy for rising PSA levels out of the undetectable range after radical prostatectomy.
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| 8. |
- Hahn, Berthold, et al.
(författare)
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Recommended practices for wind farm data collection and reliability assessment for O&M optimization
- 2017
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 137, s. 358-365
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Konferensbidrag (refereegranskat)abstract
- The paper provides a brief overview of the aims and main results of IEA Wind Task 33. IEA Wind Task 33 was an expert working group with a focus on data collection and reliability assessment for O & M optimization of wind turbines. The working group started in 2012 and finalized the work in 2016. The complete results of IEA Wind Task 33 are described in the expert group report on recommended practices for "Wind farm data collection and reliability assessment for O & M optimization" which will be published by IEA Wind in 2017. This paper briefly presents the background of the work, the recommended process to identify necessary data, and appropriate taxonomies structuring and harmonizing the collected entries. Finally, the paper summarizes the key findings and recommendations from the IEA Wind Task 33 work.
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| 9. |
- Janciauskiene, Sabina, et al.
(författare)
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Performance of enhanced liver fibrosis plasma markers in asymptomatic individuals with ZZ α1-antitrypsin deficiency.
- 2011
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Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 23:8, s. 716-720
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is a common genetic cause of chronic liver disease. According to retrospective studies, up to 25% of those with homozygous ZZ (Glu 342 to Lys) AATD suffer from liver cirrhosis and/or liver cancer in late adulthood. We hypothesized that the plasma markers for liver fibrosis, necrosis, and apoptosis may identify AATD individuals at higher risk for liver diseases. METHODS: The study cohort included 52 clinically healthy ZZ AATD individuals of 34 years of age, identified in the Swedish neonatal screening of 1972-1974, and 81 age-matched controls with normal MM AAT variant. We analyzed plasma levels of the enhanced liver fibrosis (ELF) panel, including plasma tissue inhibitor of metalloprotease-1, amino-terminal propeptide of type III collagen and hyaluronic acid (HA), and the M30 and M65 antigens, markers for apoptosis/necrosis. RESULTS: Higher levels of tissue inhibitor of metalloprotease-1 (52%, P<0.001), amino-terminal propeptide of type III collagen (12%, P<0.05), HA (17% not significant), and M65 (13.4%, P=0.043) were found in ZZ than in MM patients. In the ZZ group, plasma levels of AAT correlated with M65 (P<0.01) and with HA (P<0.05). On the basis of the ELF panel, M30 and M65, a logistic regression model enabled us to correctly classify 81.2% of the originally grouped ZZ and MM cases with a sensitivity of 73.1% and a specificity of 86.4%. CONCLUSION: The ELF markers are associated with ZZ AATD at early adulthood, and can be considered as a useful tool to identify ZZ cases at an increased risk of developing liver diseases later in life.
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| 10. |
- Jürgensen, Jan Henning, 1987-
(författare)
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Condition-based Failure Rate Modelling for Individual Components in the Power System
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The electrical power grid is one of the most important infrastructures in the modernsociety. It supplies industrial and private customers with electricity and supportsother critical infrastructures such as the water supply. Thus, it is significant that the power grid is a reliable system. However, the power system experiences a hugetransition from classical production methods such as coal and nuclear power plantsto distributed renewable energy forms such as wind energy and photovoltaic. This change to a more distributed system challenges the existing power grid as well as the traditional business models of electric utilities. Thus, cost minimization to increase profitability and improvement of the power grid to increase customer satisfactionare in the focus. One approach to increase the reliability of the grid and decrease maintenance costs is a condition-based maintenance approach which requirescondition monitoring techniques.This thesis introduces into failure rate modelling for individual power system components and develops a method to calculate individual failure rates based onthe average failure rate, failure statistics, and condition monitoring data. This approach includes the analysis of failure statistics to identify failure causes and failure locations which are population characteristics but can be utilized to describe the heterogeneity within the population. Thus, the thesis first introduces into the topic of failure analysis and heterogeneity in populations. Different factors are identified and categorized which describe the condition development of a component overtime. Then, the literature within failure rate estimation is reviewed to present the factors which are used within failure rate modelling and to outline the existingmethods which consider the individual. However, limitations are discussed which emphasize the demand for a new approach. Consequently, this thesis introduce intoa new approach for estimating the failure rate for individual components.
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