| 1. |
- Dyrskjot, Lars, et al.
(author)
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Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study
- 2017
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 461-469
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Journal article (peer-reviewed)abstract
- Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.
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| 2. |
- Hedegaard, Jakob, et al.
(author)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Journal article (peer-reviewed)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 3. |
- Hoyer, Kerstin, et al.
(author)
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Biogas upgrading - Technical Review
- 2016
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Reports (other academic/artistic)abstract
- Biogas produced by anaerobic digestion is often used in gas turbines to produceelectricity. In order to increase the value of the gas and to enable utilization of the gas in other applications, it may be advantageous to upgrade the biogas. In this way, the carbon dioxide as well as various impurities are removed and biomethane is produced. Biomethane is similar to natural gas and can be used in similar applications, e.g. fed into the natural gas grid, or as vehicle fuel. Several different biogas upgrading techniques are on the market today. Some of themmake use of the fact that carbon dioxide and methane have different solubility indifferent solvents. By choosing a solvent which has a high solubility for carbon dioxide but lets methane pass through unchanged, the carbon dioxide can be separated from the methane in biogas efficiently. Common solvents used for biogas upgrading are water, amines as well as organic solvents such as Genosorb®. The difference in adsorption behavior of carbon dioxide and methane on a surface at different pressures is used in pressure swing adsorption (PSA), which can be used to effectively separate carbon dioxide from methane. Another common biogas upgrading technique uses the fact that carbon dioxide is more likely to pass through a semi permeable barrier, e.g. a membrane, than methane. By letting biogas pass through such a membrane, the carbon dioxide can thus be removed from the gas, leaving concentrated methane in the product stream. Finally, the difference in boiling point between methane and carbondioxide may be used to separate the gases in cryogenic distillation. For this report, data on the specific investment cost was collected from companies supplying biogas upgrading plants using the above described processes. The data shows a span of investment costs, but it also shows that there is no significant general difference in investment cost between the different techniques when considering a given standard project. Also the energy consumption is rather similar for the different upgrading techniques. When deciding on a suitable biogas upgrading process, it is therefore important to rather consider other aspects. These may include the ability of the different processes to handle specific impurities present in the actual project orspecific requirements in product gas quality. Also the need for consumables such as anti-foam, chemicals for pH regulation as well as operational costs for any needed pretreatment differs between biogas upgrading processes but is of course also dependent on the pretreatment needed in a project. It is important to remember that the conclusion regarding specific investment cost in this report is related to a standard case. In a real project, where more or less pre- and posttreatment will be needed depending on the choice of upgrading technique, the investment cost for different biogas upgrading techniques will most likely differ. Biogas produced from various substrates such as agricultural residues, biological waste or sewage sludge contains low concentrations of unwanted substances, e.g. impurities, such as H2S, siloxanes, ammonia, oxygen and volatile organic carbons (VOC). H2S is separated from the methane in most biogas upgrading techniques. How efficient this removal is and thus whether it is enough to meet product gas requirements differs between the different techniques. Scrubbers using absorption in water, amines or organic solvent usually remove most of the H2S, while polishing filters are needed for membrane upgrading and PSA. When separated from the methane gas, H2S, however, ends up in a CO2 rich side stream such as stripper air where it usually needs to beremoved due to environmental legislation. If the CO2 stream is utilized, the necessity to remove H2S depends on what the gas is used for. H2S thus needs to be removed from the gas at some point in most cases, but depending on the biogas upgrading technique used, this may need to be done in the raw biogas or there may be a choice regarding where in the process to remove H2S. Siloxanes may be harmful to process equipment when present at too high concentrations. In scrubber systems the produced biomethane usually needs further drying and the main part of siloxanes are removed in the dryers. Ammonia is soluble in water and the concentrations commonly found in biogas are usually removed in the condensation which is usually part of a biogas upgrading system in order to protect the upgrading system from liquid water. Ammonia is not usually a problem in biogas upgrading systems. However, when H2S and ammonia arepresent simultaneously, it is important to prevent precipitation of compounds formed when these two react with each other. Since anaerobic digestion occurs under anaerobic conditions, e.g. with no oxygen present, the concentration of oxygen in biogas is usually low. Improper adjustment of oxygen injection systems used in order to biologically remove larger concentrations of H2S may increase the oxygen levels of the raw biogas. However, the oxygen concentration is commonly monitored carefully in biogas systems in order to minimize the explosion risk. Biomethane quality requirements when the gas is fed into a natural gas grid are currently limiting the oxygen content in biomethane to almost zero, especially in gas grids which include gas storage systems. It may therefore be necessary to remove oxygen from the product gas, or raw biogas if preferred, if the oxygen present in the raw biogas is passed to the produced biomethane. This is valid for scrubber techniques except membrane and PSAsystems which remove a significant amount of the oxygen. The product gas leaving the plant must uphold certain gas quality criteria, either set as a bilateral agreement with the transporter and/or buyer of the biomethane, which currently are based on national specifications. A new CEN standard on biogas injection of H gas quality has recently been sent to formal vote, regulating levels of minor impurities such as siloxanes and ammonia, and major ones such as hydrogen and oxygen. The minimum calorific content is specified, but the wobbe index is not. Allowed sulfur levels are still relatively high, and not including the contribution of odorization, which is still an issue handled nationally in Europe. Biomethane and compressed natural gas (CNG) delivered at the point of retail is also under standardization. There are efforts to introduce a second dedicated non-grid based grade, which will be beneficial to the sales of biomethane, since most of the parameters will easily be upheld by normal upgrading, with the exception of raw biogas containing larger amounts of siloxanes. In biogas upgrading with membrane separation, amine scrubbers and PSA, very pureCO2 can be produced. In biogas upgrading using these techniques, besides biomethane, CO2 can be produced and utilized. The most common ways to use CO2 are for the use in greenhouses, in the food and cooling industry or to utilize access electricity to let the CO2 react with H2 to produce methane, co-called power-to-gas. Power to gas constitutes a way to store access electricity in the form of gas which is gaining increased interest during recent years.
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| 4. |
- Hoyer, Kerstin, et al.
(author)
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Effects of enzyme feeding strategy on ethanol yield in fed-batch simultaneous saccharification and fermentation of spruce at high dry matter
- 2010
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In: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 3
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Journal article (peer-reviewed)abstract
- Background: To make lignocellulosic fuel ethanol economically competitive with fossil fuels, it is necessary to reduce the production cost. One way to achieve this is by increasing the substrate concentration in the production process, and thus reduce the energy demand in the final distillation of the fermentation broth. However, increased substrate concentration in simultaneous saccharification and fermentation (SSF) processes has been shown to result in reduced ethanol yields and severe stirring problems. Because the SSF medium is being continuously hydrolyzed, running the process in fed-batch mode could potentially reduce the stirring problems and lead to increased ethanol yields in high-solids SSF. Different enzyme feeding strategies, with the enzymes either present in the reactor from start-up or fed into the reactor together with the substrate, have been studied, along with the influence of the enzyme feeding strategy on the final ethanol yield and productivity. Results: In the present study, SSF was run successfully with 10% and 14% water-insoluble solids (WIS) in batch and fed-batch mode. The mixing of the material in the reactor was significantly better in fed-batch than batch mode, and similarly high or higher ethanol yields were achieved in fed-batch mode compared with batch SSF in some cases. No general trend in the dependence of ethanol yield on enzyme feeding strategy was found. Conclusions: The optimum enzyme feeding strategy appears to depend on the conditions during SSF, such as the WIS concentration and the concentration of inhibitory compounds in the SSF medium.
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| 5. |
- Hoyer, Kerstin, et al.
(author)
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Influence of fiber degradation and concentration of fermentable sugars on simultaneous saccharification and fermentation of high-solids spruce slurry to ethanol
- 2013
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In: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 6:145, s. 9-145
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Journal article (peer-reviewed)abstract
- Background: Saccharification and fermentation of pretreated lignocellulosic materials, such as spruce, should be performed at high solids contents in order to reduce the cost of the produced bioethanol. However, this has been shown to result in reduced ethanol yields or a complete lack of ethanol production. Previous studies have shown inconsistent results when prehydrolysis is performed at a higher temperature prior to the simultaneous saccharification and fermentation (SSF) of steam-pretreated lignocellulosic materials. In some cases, a significant increase in overall ethanol yield was reported, while in others, a slight decrease in ethanol yield was observed. In order to investigate the influence of prehydrolysis on high-solids SSF of steam-pretreated spruce slurry, in the present study, the presence of fibers and inhibitors, degree of fiber degradation and initial fermentable sugar concentration has been studied. Results: SSF of whole steam-pretreated spruce slurry at a solids content of 13.7% water-insoluble solids (WIS) resulted in a very low overall ethanol yield, mostly due to poor fermentation. The yeast was, however, able to ferment the washed slurry and the liquid fraction of the pretreated slurry. Performing prehydrolysis at 48°C for 22 hours prior to SSF of the whole pretreated slurry increased the overall ethanol yield from 3.9 to 62.1%. The initial concentration of fermentable sugars in SSF could not explain the increase in ethanol yield in SSF with prehydrolysis. Although the viscosity of the material did not appear to decrease significantly during prehydrolysis, the degradation of the fibers prior to the addition of the yeast had a positive effect on ethanol yield when using whole steam-pretreated spruce slurry. Conclusions: The results of the present study suggest that the increase in ethanol yield from SSF when performing prehydrolysis is a result of fiber degradation rather than a decrease in viscosity. The increased concentration of fermentable sugars at the beginning of the fermentation phase in SSF following prehydrolysis did not affect the overall ethanol yield in the present study.
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| 6. |
- Hoyer, Kerstin
(author)
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Production of Ethanol from Spruce at High Solids Concentrations - An Experimental Study on Process Development of Simultaneous Saccharification and Fermentation
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Replacing fossil fuels by biofuels such as ethanol is considered a promising alternative to reduce greenhouse gas (GHG) emissions and mitigate climate change. Biofuels produced from lignocellulosic biomass, so-called second generation biofuels, result in decreased GHG emissions and limit competition with food and animal feed production. Interest in producing ethanol from lignocellulosic biomass has therefore increased rapidly during recent years. Several pilot and demonstration plants for the biochemical conversion of lignocellulose to ethanol have been built, and the first commercial plants are planned to start large-scale production within the coming years. However, a great deal remains to be done in process development to increase the production efficiency and decrease production cost. The work presented in this thesis focuses on the biochemical conversion of spruce to ethanol, using enzymatic hydrolysis and fermentation in simultaneous saccharification and fermentation (SSF). The main aim of this work was to achieve a high ethanol concentration after fermentation, in order to reduce the energy required in distillation, thus reducing the production cost. A final ethanol concentration of 65 g/L was achieved, which is well above the 4 wt% considered to be the limit for economically feasible distillation. Furthermore, these experimental studies on the production of ethanol from spruce have contributed to a better understanding of some of the fundamental steps in the production process. Enzymatic hydrolysis and fermentation must be performed at higher solid substrate concentrations in order to increase the ethanol concentration after fermentation. In the first part of this work, it was shown that the decrease in ethanol yield in SSF with high solids concentration is a result of both increased mixing difficulty and increased inhibition of the yeast, and possibly the enzymes, due to increased levels of inhibitory substances. In the second part of the work, it was shown that the ethanol yield in high-solids SSF could be significantly increased by adding a prehydrolysis step prior to SSF. It was also shown that this positive effect on ethanol production from spruce is a result of fibre degradation rather than decreased viscosity, as often suggested when using other lignocellulosic materials such as straw and grass. The addition of a prehydrolysis step prior to SSF shifts the process from being fermentation-limited to being hydrolysis-limited. Prehydrolysis thus enhances fermentation, rather than the overall performance of hydrolysis. The initial dry matter content in SSF was increased from 5-10% water-insoluble solids (WIS) to 20% WIS. The process configuration in enzymatic hydrolysis and fermentation has been shown to significantly influence the overall ethanol yield. The highest ethanol concentration (65 g/L) with an overall ethanol yield of 72% was obtained in fed-batch SSF, where prehydrolysed steam-pretreated spruce was fed to the reactor over a period of time. Approximately a quarter of the cellulose was, however, not converted to glucose, and was thus not fermented to ethanol. There is thus further potential for improvements in the process, which could increase the ethanol concentration and yield.
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| 7. |
- Hoyer, Kerstin, et al.
(author)
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Production of fuel ethanol from softwood by simultaneous saccharification and fermentation at high dry matter content
- 2009
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In: Journal of Chemical Technology and Biotechnology. - : Wiley. - 0268-2575 .- 1097-4660. ; 84:4, s. 570-577
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Journal article (peer-reviewed)abstract
- BACKGROUND: The production of bio-ethanol from softwood is considered a promising alternative to fossil fuels in Sweden. In order to make fuel ethanol economically competitive with fossil fuels, it is important to reduce the production cost, which can be done by increasing the dry matter content of the fermentation medium, thus reducing the energy demand in the final distillation of the fermentation broth. Running simultaneous saccharification and fermentation l at higher dry matter content has, however, been found to decrease the ethanol yield. RESULTS: The use of different stirrer types and stirring speeds in the present study has shown to have an influence on the final ethanol yield in SSF with 10% water-insoluble solids (WIS). Also, higher concentration of pretreatment hydrolysate, i.e., with increased inhibitor concentration, at the same WIS resulted in a decreased ethanol yield. However, despite stirring problems and high inhibitor concentration, ethanol was produced at 12% WIS with an ethanol yield in the SSF step of 81% of the theoretical based on the content of fermentable sugars in the fermentor. CONCLUSION: The decrease in ethanol yield in SSF at high dry matter content has been shown to be a combined effect of increased mass transfer resistance and increased inhibitor concentration in the fermentation broth. (c) 2008 Society of Chemical Industry
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| 8. |
- Hoyer, Kerstin, et al.
(author)
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The effect of prehydrolysis and improved mixing on high-solids batch simultaneous saccharification and fermentation of spruce to ethanol
- 2013
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In: Process Biochemistry. - : Elsevier BV. - 1873-3298 .- 1359-5113. ; 48:2, s. 289-293
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Journal article (peer-reviewed)abstract
- In the production of ethanol from lignocellulosic material, it is necessary to reach a high ethanol concentration after fermentation. Simply increasing the substrate concentration leads to stirring problems and inhibition of the enzymes and yeast in the process. Batch simultaneous saccharification and fermentation (SSF) of steam-pretreated spruce with 13.7% water-insoluble solids (WIS) (25% total solids (TS)) was run in a stirred-tank reactor as well as in two reactors designed to handle solid or semi-solid material. In all reactors, the overall ethanol yields were only between Sand 6%. Fermentation of the liquid fraction of the steam-pretreated spruce slurry resulted in an overall ethanol yield of 85%. 22 h of prehydrolysis at 48 degrees C prior to SSF at 32 C significantly increased the overall ethanol yield to 72% (final ethanol concentration of 47.8 g/L), using the whole slurry of steam-pretreated spruce at a dry matter content of 13.7% WIS (25% TS). (C) 2013 Elsevier Ltd. All rights reserved.
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| 9. |
- Schindler, Lena, et al.
(author)
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Lifetime Trauma History and Cognitive Functioning in Major Depression and Their Role for Cognitive-Behavioral Therapy Outcome
- 2021
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In: Clinical Psychology in Europe. - : Leibniz Institute for Psychology (ZPID). - 2625-3410. ; 3:3
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Journal article (peer-reviewed)abstract
- Background: While cognitive-behavioral therapy (CBT) is the gold-standard psychological treatment for major depression (MD), non-response and lacking stability of treatment gains are persistent issues. Potential factors influencing treatment outcome might be lifetime trauma history and possibly associated primarily prefrontal-cortex- and hippocampus-dependent cognitive alterations. Method: We investigated MD and healthy control participants with (MD+T+, n = 37; MD-T+, n = 39) and without lifetime trauma history (MD+T-, n = 26; MD-T-, n = 45) regarding working memory, interference susceptibility, conflict adaptation, and autobiographical memory specificity. Further, MD+T+ (n = 21) and MD+T- groups (n = 16) were re-examined after 25 CBT sessions, with MD-T- individuals (n = 34) invited in parallel in order to explore the stability of cognitive. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License, CC BY 4.0, which permits unrestricted use, distribution, and reproduction, provided the original work is properly cited. alterations and the predictive value of lifetime trauma history, cognitive functioning, and their interaction for treatment outcome. Results: On a cross-sectional level, MD+T+ showed the highest conflict adaptation, but MD+T- the lowest autobiographical memory specificity, while no group differences emerged for working memory and interference susceptibility. Clinical improvement did not differ between groups and cognitive functioning remained stable over CBT. Further, only a singular predictive association of forward digit span, but no other facets of baseline cognitive functioning, lifetime trauma history, or their interaction with treatment outcome emerged. Discussion: These results indicate differential roles of lifetime trauma history and psychopathology for cognitive functioning in MD, and add to the emerging literature on considering cognitive, next to clinical remission as a relevant treatment outcome.
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