| 1. |
- Neovius, Martin, et al.
(författare)
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Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.
- 2018
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Ingår i: The lancet. Diabetes & endocrinology. - : Elsevier. - 2213-8595 .- 2213-8587. ; 6:3, s. 197-207
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment.Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts.During 68528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome.Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health.US National Institutes of Health and Swedish Research Council.
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| 2. |
- Sjöholm, Kristoffer, et al.
(författare)
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Targeted proteomics and absolute protein quantification for the construction of a stoichiometric host-pathogen surface density model
- 2017
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Ingår i: Molecular and Cellular Proteomics. - 1535-9476. ; 16:4, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is a systemic immune response responsible for considerable morbidity and mortality. Molecular modeling of host-pathogen interactions in the disease state represents a promising strategy to define molecular events of importance for the transition from superficial to invasive infectious diseases. Here we used the Gram-positive bacterium Streptococcus pyogenes as a model system to establish a mass spectrometry based workflow for the construction of a stoichiometric surface density model between the S. pyogenes surface, the surface virulence factor M-protein, and adhered human blood plasma proteins. The workflow relies on stable isotope labeled reference peptides and selected reaction monitoring mass spectrometry analysis of a wild-type strain and an M-protein deficient mutant strain, to generate absolutely quantified protein stoichiometry ratios between S. pyogenes and interacting plasma proteins. The stoichiometry ratios in combination with a novel targeted mass spectrometry method to measure cell numbers enabled the construction of a stoichiometric surface density model using protein structures available from the protein data bank. The model outlines the topology and density of the hostpathogen protein interaction network on the S. pyogenes bacterial surface, revealing a dense and highly organized protein interaction network. Removal of the M-protein from S. pyogenes introduces a drastic change in the network topology, validated by electron microscopy. We propose that the stoichiometric surface density model of S. pyogenes in human blood plasma represents a scalable framework that can continuously be refined with the emergence of new results. Future integration of new results will improve the understanding of protein-protein interactions and their importance for bacterial virulence. Furthermore, we anticipate that the general properties of the developed workflow will facilitate the production of stoichiometric surface density models for other types of host-pathogen interactions.
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| 3. |
- Ahlén Bergman, Emma, et al.
(författare)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 7. |
- Brackmann, Christian, et al.
(författare)
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Picosecond excitation for reduction of photolytic effects in two-photon laser-induced fluorescence of CO
- 2013
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 34, s. 3541-3548
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon laser-induced fluorescence for detection of carbon monoxide (CO) frequently shows interferences by emission from photolytically produced C-2 radicals encountered under fuel-rich combustion conditions. Reduced C-2 interference for excitation with laser pulses in the picosecond regime is here demonstrated by comparison with excitation using nanosecond pulses for measurements in laminar premixed ethene-air flames. Compared with nanosecond pulses of 8 ns duration and 4 mJ pulse energy, picosecond pulses of 80 ps duration and around 0.5 mJ pulse energy gave similar to 10 times higher peak power, which allowed for efficient CO excitation and resulted in stronger signal with lower C-2 interference. CO fluorescence with picosecond excitation showed a linear to quadratic power dependence, indicating photoionization, whereas a more quadratic dependence was found for the C-2 interference. A sub-nanosecond effective lifetime of CO resulted in a rapid fluorescence decay compared with C-2 and allowed for efficient reduction in C-2 interference by minimizing the detection gate. In addition, interference compensation using time-resolved detection could be demonstrated. Altogether, picosecond pulses provide efficient two-photon excitation of CO in terms of signal strength as well as reduced C-2 interference. (C) 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 8. |
- Bruze, Gustaf, et al.
(författare)
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Associations of Bariatric Surgery With Changes in Interpersonal Relationship Status Results From 2 Swedish Cohort Studies
- 2018
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Ingår i: JAMA Surgery. - : American Medical Association. - 2168-6254 .- 2168-6262. ; 153:7, s. 654-661
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Bariatric surgery is a life-changing treatment for patients with severe obesity, but little is known about its association with interpersonal relationships.OBJECTIVES: To investigate if relationship status is altered after bariatric surgery.DESIGN, SETTING, AND PARTICIPANTS: Changes in relationship status after bariatric surgery were examined in 2 cohorts: (1) the prospective Swedish Obese Subjects (SOS) study, which recruited patients undergoing bariatric surgery from September 1, 1987, to January 31, 2001, and compared their care with usual nonsurgical care in matched obese control participants; and (2) participants from the Scandinavian Obesity Surgery Registry (SOReg), a prospective, electronically captured register that recruited patients from January 2007 through December 2012 and selected comparator participants from the general population matched on age, sex, and place of residence. Data was collected in surgical departments and primary health care centers in Sweden. The current analysis includes data collected up until July 2015 (SOS) and December 2012 (SOReg). Data analysis was completed from June 2016 to December 2017.MAIN OUTCOMES AND MEASURES: In the SOS study, information on relationship status was obtained from questionnaires. In the SOReg and general population cohort, information on marriage and divorce was obtained from the Swedish Total Population Registry.RESULTS: The SOS study included 1958 patients who had bariatric surgery (of whom 1389 [70.9%] were female) and 1912 matched obese controls (of whom 1354 [70.8%] were female) and had a median (range) follow-up of 10 (0.5-20) years. The SOReg cohort included 29 234 patients who had gastric bypass surgery (of whom 22 131 [75.6%] were female) and 283 748 comparators from the general population (of whom 214 342 [75.5%] were female), and had a median (range) follow-up of 2.9 (0.003-7.0) years. In the SOS study, the surgical patients received gastric banding (n = 368; 18.8%), vertical banded gastroplasty (n = 1331; 68.0%), or gastric bypass (n = 259; 13.2%); controls received usual obesity care. In SOReg, all 29 234 surgical participants received gastric bypass surgery. In the SOS study, bariatric surgery was associated with increased incidence of divorce/separation compared with controls for those in a relationship (adjusted hazard ratio [aHR] = 1.28; 95% CI, 1.03-1.60; P =.03) and increased incidence of marriage or new relationship (aHR = 2.03; 95% CI, 1.52-2.71; P <.001) in those who were unmarried or single at baseline. In the SOReg and general population cohort, gastric bypass was associated with increased incidence of divorce compared with married control participants (aHR = 1.41; 95% CI, 1.33-1.49; P <.001) and increased incidence of marriage in those who were unmarried at baseline (aHR = 1.35; 95% CI, 1.28-1.42; P <.001). Within the surgery groups, changes in relationship status were more common in those with larger weight loss.CONCLUSIONS AND RELEVANCE: In addition to its association with obesity comorbidities, bariatric surgery-induced weight loss is also associated with changes in relationship status.
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| 9. |
- Christenson, Karin, et al.
(författare)
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Endogenous Acute Phase Serum Amyloid A Lacks Pro-Inflammatory Activity, Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors.
- 2013
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2) that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1) both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2). We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.
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| 10. |
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Culture, Creativity and Economy : Collaborative Practices, Value Creation and Spaces of Creativity
- 2021
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- This book nuances our understanding of the contemporary creative economy by engaging with a set of three key tensions which emerged over the course of eight European Colloquiums on Culture, Creativity and Economy (CCE): 1) the tension between individual and collaborative creative practices, 2) the tension between tradition and innovation, and 3) the tension between isolated and interconnected spaces of creativity.Rather than focusing on specific processes, such as production, industries or locations, the tensions acknowledge and engage with the messy and restless nature of the creative economy. Individual chapters offer insights into poorly understood practices, locations and contexts such as co-working spaces in Berlin and rural Spain, creative businesses in Leicester and the role and importance of cultural intermediaries in creative economies within Africa. Others examine the nature of trans-local cultural flows, the evolving "field" of fashion, and the implications of social media and crowdfunding platforms.This book will be of interest to students, scholars and professionals researching the creative economy, as well as specific cultural and creative industries, across the humanities and social sciences.
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