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1.
  • Chew, Michelle S., et al. (author)
  • Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
  • 2022
  • In: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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2.
  • Strittmatter, Frank, et al. (author)
  • Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms
  • 2011
  • In: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 650:2-3, s. 650-655
  • Journal article (peer-reviewed)abstract
    • Thromboxane A(2) (TXA(2)) induces contraction in different smooth muscle types via its receptor (TXA(2) receptor). However, any motoric role of TXA(2) in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA(2) induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA(2) analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA(2) synthase and TXA(2) receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA(2) was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). TXA(2) synthase and TXA(2) receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA(2) synthase in prostate tissue was located to glandular cells, while prostate TXA(2) receptors were located to smooth muscle and glandular cells. The stable TXA(2) metabolite TXB(2) was detected by enzyme immunoassay in the prostate. TXA(2) induces contraction of isolated human prostate tissue by TXA(2) receptor activation. Prostate smooth muscle TXA(2) receptors are coupled to Rho kinase and Ca(2+)-dependent mechanisms. The distribution of TXA(2) synthase and TXA(2) receptors in the human prostate suggests TXA(2)-mediated paracrine epithelial-stromal interactions.
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3.
  • Andersson, Christian H., et al. (author)
  • Mathematical understanding of training data and AI : a lesson plan for critical thinking and ethical perspectives
  • 2024
  • In: Proceedings / Actes CIEAEM 74. - Palermo, Italy. ; , s. 681-685
  • Conference paper (peer-reviewed)abstract
    • AI and machine learning are increasingly being applied to solve complex societal issues. One approach is to train algorithms on training data that describes human behavior. This is not without potential problems though. For example, historical human behavior may contain biases, and then algorithms may reproduce social injustices. This workshop contained lesson elements from a study where pre-service mathematics teachers conducted lessons to first conceptually teach how mathematical modelling based on machine learning works, and then to broaden the scope to consider critical thinking in relation to ethics and democratic values. The participants were invited to test and discuss the lesson elements.
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4.
  • Andersson, Christian X, 1973, et al. (author)
  • Shedding and gamma-Secretase mediated intramembrane proteolysis of the mucin-type molecule CD43
  • 2005
  • In: Biochem J.. ; 387:2, s. 377-384
  • Journal article (peer-reviewed)abstract
    • CD43 is a transmembrane molecule that contains a 123-aminoacids-long cytoplasmic tail and a highly O-glycosylated extracellular domain of mucin type. Endogenous CD43 expressed in COLO 205, K562 and Jurkat cells revealed a membrane-associated, 20 kDa CD43-specific cytoplasmic tail fragment (CD43-CTF) upon inhibition of gamma-secretase. This fragment was formed by an extracellular cleavage, as it was not accumulated after treating cells with 1,10-phenanthroline, a metalloprotease inhibitor. When CD43 was transfected into HEK-293 cells expressing dominant-negative PS1 (presenilin-1), the CD43-CTF was accumulated, but not in cells with wild-type PS1. Owing to its accumulation in the presence of a non-functional PS variant, it may thus be a novel gamma-secretase substrate. This CTF is formed by an extracellular cleavage close to the membrane, is a fragment that can be concluded to be a substrate for gamma-secretase. However, the intracellular gamma-secretase product has not been possible to detect, suggesting a quick processing of this product. During normal growth the CTF was not found without gamma-secretase inhibition, but when the cells (COLO 205) were very confluent the fragment could be detected. The intracellular domain of CD43 has previously been shown to contain a functional nuclear localization signal, and has been suggested to be involved in gene activation. From this and the present results, a novel way to explain how mucin-type molecules may transduce intracellular signals can be proposed.
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5.
  • Andersson, Erik, et al. (author)
  • A Randomized Controlled Trial of Guided Internet-delivered Cognitive Behavioral Therapy for Erectile Dysfunction
  • 2011
  • In: Journal of Sexual Medicine. - : Wiley-Blackwell. - 1743-6095 .- 1743-6109. ; 8:10, s. 2800-2809
  • Journal article (peer-reviewed)abstract
    • Introduction. Men with erectile dysfunction are often worried about their condition, have interpersonal difficulties, and have a reduced quality of life. Internet-delivered cognitive behavior therapy (ICBT) has been shown effective for a number of health problems but evidence is limited concerning the treatment of erectile dysfunction. less thanbrgreater than less thanbrgreater thanAim. The study investigated the effects of ICBT for erectile dysfunction. less thanbrgreater than less thanbrgreater thanMethods. Seventy-eight men were included in the study and randomized to either ICBT or to a control group, which was an online discussion group. Treatment consisted of a 7-week Web-based program with e-mail-based therapist support. Each therapist spent an average of 55 minutes per participant. less thanbrgreater than less thanbrgreater thanMain Outcome Measure. The International Index of Erectile Functioning five-item version was administered via the telephone at pretreatment, post-treatment, and 6 months after receiving ICBT. less thanbrgreater than less thanbrgreater thanResults. At post-treatment, the treatment group had significantly greater improvements with regard to erectile performance compared with the control group. Between-group differences at post-treatment were small (d = 0.1), but increased at the 6-month follow-up (d = 0.88). less thanbrgreater than less thanbrgreater thanConclusions. This study provides support for the use of ICBT as a possible treatment format for erectile dysfunction.
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6.
  • Andersson, Erik, et al. (author)
  • Cost-effectiveness of an internet-based booster program for patients with obsessive-compulsive disorder : Results from a randomized controlled trial
  • 2015
  • In: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 14-19
  • Journal article (peer-reviewed)abstract
    • Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066-1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000-1050 the first year, but this figure grew considerably after two years ($2500-5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years. (C) 2014 Elsevier Inc. All rights reserved.
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7.
  • Andersson, Erik, et al. (author)
  • Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial
  • 2011
  • In: BMC Public Health. - : BioMed Central. - 1471-2458. ; 11:215
  • Journal article (peer-reviewed)abstract
    • Background: Irritable Bowel Syndrome (IBS) is highly prevalent and is associated with a substantial economic burden. Cognitive behavior therapy (CBT) has been shown to be effective in treating IBS. The aim of this study was to evaluate the cost-effectiveness of a new treatment alternative, internet-delivered CBT based on exposure and mindfulness exercises. Methods: Participants (N = 85) with IBS were recruited through self-referral and were assessed via a telephone interview and self-report measures on the internet. Participants were randomized to internet-delivered CBT or to a discussion forum. Economic data was assessed at pre-, post- and at 3-month and 1 year follow-up. Results: Significant cost reductions were found for the treatment group at $16,806 per successfully treated case. The cost reductions were mainly driven by reduced work loss in the treatment group. Results were sustained at 3-month and 1 year follow-up. Conclusions: Internet-delivered CBT appears to generate health gains in IBS treatment and is associated with cost-savings from a societal perspective.
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8.
  • Andersson, Erik, et al. (author)
  • Cost-effectiveness of internet-based cognitive behavior therapy for obsessive-compulsive disorder : results from a randomized controlled trial
  • 2015
  • In: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 47-53
  • Journal article (peer-reviewed)abstract
    • Obsessive-compulsive disorder (OCD) is a common and disabling disorder. Although evidence-based psychological treatments exists, such as cognitive behavior therapy (CBT), the cost-effectiveness of CBT has not been properly investigated. In this trial, we used health economic data from a recently conducted randomized controlled trial, where 101 OCD patients were allocated to either internet-based CBT (ICBT) or control condition (online support therapy). We analyzed treatment effectiveness in relation to costs, using both a societal- (including all direct and indirect costs) and a health care unit perspective (including only the direct treatment costs). Bootstrapped net benefit regression analyses were also conducted, comparing the difference in costs and effects between ICBT and control condition, with different willingness-to-pay scenarios. Results showed that ICBT produced one additional remission for an average societal cost of $931 and this figure was even lower ($672) when narrowing the perspective to treatment costs only. The cost-utility analysis also showed that ICBT generated one additional QALY to an average price of $7186 from a societal perspective and $4800 when just analyzing the treatment costs. We conclude that ICBT is a cost-effective treatment and the next step in this line of research is to compare the cost-effectiveness of ICBT with face-to-face CBT. (C) 2014 Elsevier Inc. All rights reserved.
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9.
  • Andersson, Erik, et al. (author)
  • d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants A Randomized Clinical Trial
  • 2015
  • In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 72:7, s. 659-667
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t(62) = -3.00; P = .004; and t(61) = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
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10.
  • Andersson, Evelyn, et al. (author)
  • Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
  • 2013
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
  • Journal article (peer-reviewed)abstract
    • ObjectiveThe role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.MethodParticipants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.ResultsAt long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.ConclusionsNone of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.
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11.
  • Andersson, Erik, et al. (author)
  • Internet-based cognitive behavior therapy for obsessive compulsive disorder: A pilot study
  • 2011
  • In: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 11:125
  • Journal article (peer-reviewed)abstract
    • Background: Cognitive behavior therapy (CBT) is widely regarded as an effective treatment for obsessive compulsive disorder (OCD), but access to CBT therapists is limited. Internet-based CBT (ICBT) with therapist support is a way to increase access to CBT but has not been developed or tested for OCD. The aim of this study was to evaluate ICBT for OCD. less thanbrgreater than less thanbrgreater thanMethod: An open trial where patients (N = 23) received a 15-week ICBT program with therapist support consisting of psychoeducation, cognitive restructuring and exposure with response prevention. The primary outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), which was assessed by a psychiatrist before and immediately after treatment. Secondary outcomes were self-rated measures of OCD symptoms, depressive symptoms, general functioning, anxiety and quality of life. All assessments were made at baseline and post-treatment. less thanbrgreater than less thanbrgreater thanResults: All participants completed the primary outcome measure at all assessment points. There were reductions in OCD symptoms with a large within-group effect size (Cohens d = 1.56). At post-treatment, 61% of participants had a clinically significant improvement and 43% no longer fulfilled the diagnostic criteria of OCD. The treatment also resulted in statistically significant improvements in self-rated OCD symptoms, general functioning and depression. less thanbrgreater than less thanbrgreater thanConclusions: ICBT with therapist support reduces OCD symptoms, depressive symptoms and improves general functioning. Randomized trials are needed to confirm the effectiveness of this new treatment format.
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12.
  • Andersson, Erik, et al. (author)
  • Long-term efficacy of Internet-based cognitive behavior therapy for obsessive-compulsive disorder with or without booster : a randomized controlled trial
  • 2014
  • In: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 44:13, s. 2877-2887
  • Journal article (peer-reviewed)abstract
    • Background. As relapse after completed cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) is common, many treatment protocols include booster programs to improve the long-term effects. However, the effects of booster programs are not well studied. In this study, we investigated the long-term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or without an Internet-based booster program. Method. A total of 101 participants were included in the long-term follow-up analysis of ICBT. Of these, 93 were randomized to a booster program or no booster program. Outcome assessments were collected at 4, 7, 12 and 24 months after receiving ICBT. Results. The entire sample had sustained long-term effects from pre-treatment to all follow-up assessments, with large within-group effect sizes (Cohen's d=1.58-2.09). The booster group had a significant mean reduction in OCD symptoms compared to the control condition from booster baseline (4 months) to 7 months, but not at 12 or 24 months. Participants in the booster group improved significantly in terms of general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan-Meier analysis also indicated a significantly slower relapse rate in the booster group. Conclusions. The results suggest that ICBT has sustained long-term effects and that adding an Internet-based booster program can further improve long-term outcome and prevent relapse for some OCD patients.
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13.
  • Andersson, Erik, et al. (author)
  • Predictors and moderators of Internet-based cognitive behavior therapy for obsessive-compulsive disorder : Results from a randomized trial
  • 2015
  • In: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 1-7
  • Journal article (peer-reviewed)abstract
    • Internet-based cognitive behavior therapy (ICBT) for obsessive-compulsive disorder (OCD) has shown efficacy in randomized trials but many patients do not respond to the treatment, we therefore need to find predictors and moderators of treatment response. In this study, we analyzed predictors of ICBT response using both post-treatment as well as 24-month outcome data. As half of the participants were randomized to receive an Internet-based booster program as an adjunct to ICBT, we also investigated moderators of ICBT with or without booster. Results showed that more severe baseline OCD symptoms predicted worse end state outcome but also higher degree of change. Furthermore, high degree of working alliance predicted better outcome but patients with primary disgust emotions had worse treatment effects. The moderator analysis also indicated that scoring high on the obsessing subscale on the Obsessive-Compulsive Inventory-Revised predicted worse treatment outcome in the booster group. In conclusion, there are some possible predictors and moderators of ICBT for OCD but more research is needed with larger and clinically representative samples. (C) 2014 Elsevier Inc. All rights reserved.
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14.
  • Andersson, Erik, et al. (author)
  • Testing the Mediating Effects of Obsessive Beliefs in Internet-Based Cognitive Behaviour Therapy for Obsessive-Compulsive Disorder : Results from a Randomized Controlled Trial
  • 2015
  • In: Clinical Psychology and Psychotherapy. - : Wiley-Blackwell. - 1063-3995 .- 1099-0879. ; 22:6, s. 722-732
  • Journal article (peer-reviewed)abstract
    • Although cognitive interventions for obsessive-compulsive disorder (OCD) have been tested in randomized trials, there are few trials that have tested the specific mechanisms of cognitive interventions, i.e. how they achieve their effects. In this study, we aimed to investigate the mediating effects of a short cognitive intervention in the treatment of OCD and used data from a recently conducted randomized controlled trial where 101 participants were allocated to either Internet-based CBT (ICBT) or to a control condition. Obsessive beliefs were measured at pre-treatment, at the time they had received the cognitive intervention, and also at post-treatment. Weekly OCD symptoms were measured throughout the 10 weeks of treatment. We hypothesized that (1) the ICBT group would have greater reductions in obsessive beliefs (controlling for change in OCD symptoms) after completing the cognitive intervention, and that (2) this reduction would, in turn, predict greater OCD symptom reduction throughout the rest of the treatment period. Contrary to our expectations, the longitudinal mediation analysis indicated that (1) being randomized to ICBT actually increased the degree of obsessive beliefs after receiving the cognitive intervention at weeks 1-3, and (2) increase in obsessive beliefs predicted better outcome later in treatment. However, when repeating the analysis using cross-sectional data at post-treatment, the results were in line with the initial hypotheses. Results were replicated when the control condition received ICBT. We conclude that, although obsessive beliefs were significantly reduced at post-treatment for the ICBT group, early increase rather than decrease in obsessive beliefs predicted favourable outcome. Copyright (C) 2014 John Wiley & Sons, Ltd.
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15.
  • Andersson, Ellen, et al. (author)
  • Treatment with anti-factor VIIa in acute pancreatitis in rats: Blocking both coagulation and inflammation?
  • 2007
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:6, s. 765-770
  • Journal article (peer-reviewed)abstract
    • Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active- siteinactivated factor VIIa, have shown anti- inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome ( MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N- acetyl- cysteine and active- site- inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL- 6 and MIP- 2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N- acetylcysteine and active- site- inactivated factor VIIa. Levels of interleukin- 6 and macrophage inflammatory protein- 2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N- acetylcysteine and active- site- inactivated factor VIIa showed powerful antiinflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.
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16.
  • Andersson, Mattias, 1985, et al. (author)
  • Additive-like amounts of HDPE prevent creep of molten LDPE: Phase-behavior and thermo-mechanical properties of a melt-miscible blend
  • 2017
  • In: Journal of Polymer Science, Part B: Polymer Physics. - : Wiley. - 1099-0488 .- 0887-6266. ; 55:2, s. 146-156
  • Journal article (peer-reviewed)abstract
    • Low-density polyethylene (LDPE) is the preferred type of polyolefin for many medical and electrical applications because of its superior purity and cleanliness. However, the inferior thermo-mechanical properties as compared to, for example, high-density polyethylene (HDPE), which arise because of the lower melting temperature of LDPE, constitute a significant drawback. Here, we demonstrate that the addition of minute amounts of HDPE to a LDPE resin considerably improves the mechanical integrity above the melting temperature of LDPE. A combination of dynamic mechanical analysis and creep experiments reveals that the addition of as little as 1 to 2 wt% HDPE leads to complete form stability above the melting temperature of LDPE. The investigated LDPE/HDPE blend is found to be miscible in the melt, which facilitates the formation of a solid-state microstructure that features a fine distribution of HDPE-rich lamellae. The absence of creep above the melting temperature of LDPE is rationalized with the presence of tie chains and trapped entanglements that connect the few remaining crystallites.
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17.
  • Andersson, Mattias, 1985, et al. (author)
  • Dielectric strength of γ-radiation cross-linked, high vinyl-content polyethylene
  • 2015
  • In: European Polymer Journal. - : Elsevier BV. - 0014-3057. ; 64, s. 101-107
  • Journal article (peer-reviewed)abstract
    • We explore γ-radiation cross-linking of high vinyl-content low-density polyethylene (LDPE) and its potential use as a high-voltage insulation material. Of the three investigated resins containing 1, 0.5 and 0.17 vinyl groups per 1000 carbons, respectively, only the highest vinyl-content material featured a sufficiently high gel content of more than 70% and hot-set elongation below 175%, when cross-linked with a γ-radiation dose of at least 68 kGy. Differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) reveal that neither the crystallinity nor the lamellar thickness of the highest vinyl-content LDPE are negatively affected by γ-radiation cross-linking. As a result, we find that the dielectric strength, as characterized by electrical tree initiation experiments, can be maintained upon γ-radiation cross-linking.
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18.
  • Andersson, Mattias, 1985, et al. (author)
  • Highly Insulating Polyethylene Blends for High-Voltage Direct-Current Power Cables
  • 2017
  • In: ACS Macro Letters. - : American Chemical Society (ACS). - 2161-1653. ; 6:2, s. 78-82
  • Journal article (peer-reviewed)abstract
    • The insulation of state-of-the-art extruded high-voltage direct-current (HVDC) power cables is composed of cross-linked low-density polyethylene. Driven by the search for sustainable energy solutions, concepts that improve the ability to withstand high electrical fields and, ultimately, the power transmission efficiency are in high demand. The performance of a HVDC insulation material is limited by its residual electrical conductivity. Here, we demonstrate that the addition of small amounts of high-density polyethylene (HDPE) to a low-density polyethylene (LDPE) resin results in a drastic reduction in DC conductivity. An HDPE content as low as 1 wt % is found to introduce a small population of thicker crystalline lamellae, which are finely distributed throughout the material. The change in nanostructure correlates with a decrease in DC conductivity by approximately 1 order of magnitude to about 10(-15) S m(-1) at high electric fields of 30 and 40 kV mm(-1) and elevated temperature of 70 degrees C. This work opens up an alternative design concept for the insulation of HVDC power cables.
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19.
  • Andersson, Mattias, 1985, et al. (author)
  • Influence of Molecular Weight on the Creep Resistance of Almost Molten Polyethylene Blends
  • 2018
  • In: Macromolecular Chemistry and Physics. - : Wiley. - 1022-1352 .- 1521-3935. ; 219:3
  • Journal article (peer-reviewed)abstract
    • The most common route to improve the creep resistance of low density polyethylene (LDPE) is crosslinking, which however results in volatile decomposition products that must be removed. Blends of LDPE and an additive-like amount of a linear polyethylene are found to offer improved creep resistance. Above the melting temperature of LDPE, T m ≈ 111 °C, a load-bearing network of higher-melting crystallites—connected through tie chains and trapped entanglements—provides additional form stability. The molecular weight of the linear polyethylene is found to be critical for the ability to arrest creep, which is correlated with the probability of tie chain formation as well as cocrystallization of the two polyethylenes. A number of high-density polyethylenes (HDPE) and one ultrahigh molecular weight polyethylene (UHMW-PE) are explored. For blends of LDPE and 2 wt% of the linear polyethylene, an HDPE with a weight-average molecular weight M w of 16 kg mol −1 is found to be sufficient to arrest creep at 115 °C. Further improvement in terms of creep resistance is obtained in case of UHMW-PE with creep fracture occurring only at a stress of 12 kPa at 115 °C. (Figure presented.).
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20.
  • Andersson, Mattias, 1985, et al. (author)
  • Invariant Dielectric Strength upon Addition of Low Amounts of HDPE to LDPE
  • 2016
  • In: Annual Report - Conference on Electrical Insulation and Dielectric Phenomena, CEIDP. - 0084-9162. ; 2016-December, s. 711-714
  • Conference paper (peer-reviewed)abstract
    • Blending of polyethylenes permits to combine the superior mechanical properties of high-density material with the higher purity that is associated with low-density resins. Mixing different polyethylene architectures offers a lot of advantages, but for electrical applications it is important that there is no detrimental effect on the resulting dielectric strength. Here, the nanostructure of crosslinked blends that comprise low-and high-density polyethylene (LDPE and HDPE) is explored. Despite the presence of higher-melting lamellae the formation of electrical trees under alternating current (AC) conditions is found to be invariant for the investigated HDPE content of 1 to 10 wt%. This observation suggests that the use of polyethylene blends is feasible for AC electrical applications.
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21.
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22.
  • Andersson, Sofia Lovisa, et al. (author)
  • Long term trials with membrane bioreactor for enhanced wastewater treatment coupled with compact sludge treatment -pilot Henriksdal 2040, results from 2020
  • 2021
  • Reports (other academic/artistic)abstract
    • Stockholm’s wastewater treatment plant (WWTP) in is currently retrofitting from a conventional activated sludge process to a new membrane bioreactor (MBR) process. It also includes new treatment steps for sludge handling. Stockholm Vatten och Avfall (SVOA) and IVL have since 2014 conducted long-term MBR studies in pilot scale at the R&D facility Hammarby Sjöstadsverk. This report present results from the pilot operation during 2020. The MBR-pilot was continuously operated at a higher inflow than the design average flow. The average effluent concentration of nitrogen and phosphorus met the effluent requirements of the future WWTP also this year. A low consumption of phosphorus precipitation chemicals could be achieved mainly due to a high Bio-P activity. The pilot showed that glycerol can be a good temporary carbon source at Henriksdal WWTP during startup. Like previous years, the membranes in membrane tank 1 (MT1) was cleaned with oxalic acid and the membranes in MT2 with citric acid. Several tests to optimize the chemical consumption for membrane cleaning were performed. Recovery cleanings (RC) of the membranes were performed twice in 2020.In the sludge pilot, a thermophilic and a mesophilic hydraulic retention time (HRT) crash test showed stable performance down to 4 days HRT. The overall resource consumption in the pilot showed that the optimization of phosphorus precipitation and membrane cleaning chemicals resulted in a significantly lower dosing than design values for the future Henriksdal WWTP. 
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23.
  • Andersson, Sofia Lovisa, et al. (author)
  • Långtidsförsök med membranbioreaktor för förbättrad avloppsvattenrening i kombination med kompakt slambehandling
  • 2023
  • Reports (other academic/artistic)abstract
    • Henriksdals reningsverk i Stockholm byggs nu ut och om för ökad kapacitet (från 0,8 till 1,6 miljoner PE) och för förbättrad reningsgrad (6 mg TN/l, 0,20 mg TP/L, 5 mg BOD7/l). Projektet inkluderar uppgradering av den befintliga konventionella aktivslamprocessen till en ny membranbioreaktorprocess (MBR) med mer än 1,6 m2 installerad membranyta.Det inkluderar även utökad förbehandling och ett nytt steg för primärslamförtjockning. Termofil rötning av tjockt slam (~6 % TS) vid hög organisk belastning och relativt låg uppehållstid kommer ersätta dagens mesofila rötning.För att öka kunskapen om MBR-teknik i nordiskt klimat har Stockholm Vatten och Avfall (SVOA) och IVL Svenska Miljöinstitutet genomfört långtidsstudier på en membranprocess i pilotskala på FoU-anläggningen Hammarby Sjöstadsverk, som ligger i anslutning till Henriksdals reningsverk. MBR-piloten togs i drift 2013 och byggdes om till sin nuvarande utformning under 2016. År 2017 kompletterades MBR-piloten med en slamlinje för att kunna studera olika aspekter av slamrötning.Under 2021 kördes MBR-piloten med ett fast inflöde på 4,1 m3/h, vilket är 37 % högre än det designade medelflödet, med externt tillförskaffad glycerol och internt producerad VFA-kolkälla för efterdenitrifikation.Aluminium (PAX) användes i stället för trevärt järn (PIX) som komplement till tvåvärt järn (FeSO4) för fosforutfällning. Detta gjordes för att testa driftstrategin för den första MBR-linjen i Henriksdals reningsverk. Medelhalter av kväve och fosfor i utgående vatten var 3,9 mg TN/L respektive 0,07 mg TP/L, vilket innebär att utsläppsvärden uppfylldes även i år. För att uppnå detta krävdes 8,6 g Fe2+/m3 och 0,9 g Al3+/m3.Under försök med fluxförhöjare tillsattes totalt 17,8 g järn (Fe2++ Fe3+)/m3. Glyceroldosen motsvarade 17,3 g COD/m3, och för användning av internt producerad VFA motsvarande dosen 15,5 g COD/m3. Den något högre förbrukningen av fosforfällningskemikalier jämfört med 2020, 1,29 mol metall per mol avlägsnad fosfor, berodde främst på en lägre bio-P aktivitet under 2021. År 2021 var fosforsläppshastigheten mycket låg under våren, ex. < 1 g PO4-P/kg VSS,h i juni men återhämtade sig under sommaren med t.ex. 5,5 g PO4-P/kg VSS,h i juli, efter att doseringen av skumdämpare stoppades.Järn- och aluminiumhalten i det aktiva slammet var 6,2 respektive 0,7 %. Genomsnittlig total slamålder under 2021 var 17,2 dagar och luftad medelslamålder var 7 dagar. Nitrifikation var alltid komplett med utgående ammoniumkoncentrationer under 2 mg/L, förutom vecka 25.Tester med användning av internt producerad VFA som kolkälla visade att den specifika COD-förbrukningen var nästan densamma som för glycerol när man jämförde årsgenomsnittet från 2021 och 2020. Utgående nitrat och total kvävereduktion var liknande under försöket med VFA som resten av året, då glycerol användes.Liksom tidigare år rengjordes membranen i membrantank 1 (MT1) med oxalsyra och membranen i MT2 med citronsyra. Båda membranen rengjordes också med natriumhypoklorit. Membranen kördes med ett genomsnittligt flux på 21 till 25 L/(m2·h), men med startvecka 25 testades fullskaledesignens maximala nettoflux på 30 L/(m2·h) i piloten under 25 veckor. Netto-TMP varierade mellan 49 och 218 mbar för MT1 och mellan 51 och 146 mbar för MT2. TMP reducerades efter varje återhämtningsrengöring (RC) med hypoklorit, men effekten varade inte länge. Permeabiliteten var generellt över 200 L/(m2·h·bar) under hela 2021–2022 för båda membranen. Återhämtningsrengöringar gjordes två gånger med hypoklorit och en gång med syror under 2021. Under 2022 genomfördes en slutlig RC, först med hypoklorit sedan med syror. Den första RC för MT1 resulterade i en tydlig ökning av permeabiliteten efter rengöring. För MT2 var den största ökningen av permeabiliteten resultatet av en citronsyra-MC (en vecka efter hypoklorit-RC).Följande RC i slutet av 2021 och i mars 2022 hade tydliga men mindre positiva inverkan på permeabiliteten. Före den första RC var permeabiliteten högre för MT1 (rengöras med oxalsyra) jämfört med MT2 (rengöras med citronsyra). Efter de första RC hade båda membranen liknande permeabilitet. Som ett resultat av den tuffa driftstrategin från vecka 25 2021 minskade permeabiliteten ganska snabbt efter RC. MT2 nådde en stabil nivå runt 250-300 L/(m2·h·bar) medan MT1 sjönk ytterligare till som lägst 200 L/(m2·h·bar).Utsläpp av klorerade föreningar mättes under den slutliga återställningsrengöringen med natriumhypoklorit. Utsläppsprocessen var långsammare än förväntat och generellt sett observerades inga tydliga tecken på dämpning av utsläppen under provtagningens 21 timmar. Även om sammansatta prover på flera timmar under natten inte ger tillräckligt med detaljer, drogs slutsatsen att utsläppen kan vara skadliga under hela RC-processen ur ett exponeringsperspektiv. Exempelvis nådde trikloramin sin topp vid 36 gånger den rekommenderade gränsen, klorgas vid 73 % av korttidsexponeringsgränsen (15 min exponering) och kloroform vid 9 % av den yrkesmässiga exponeringsgränsen (genomsnittlig arbetsdag på 8 timmar).För att följa upp tidigare mätningar av växthusgaserna lustgas (N2O) och metan (CH4) genomfördes en ny mätkampanj under flera månader i 2021. Generellt sett var utsläppen som observerades 2021 betydligt högre än i tidigare kampanjer och särskilt höga N2O-utsläpp från membrantanken kunde observeras. Någon tydlig orsak kunde inte identifieras men den högre inkommande belastningen med bibehållna reningskrav och ett "bättre" provtagningsupplägg kan delvis vara en förklaring.I samarbete med Kemira genomfördes tester med en fluxförhöjande produkt (flux enhancer). Ingen uppenbar positiv eller negativ förändring i permeabiliteten på grund av dosering av fluxförhöjare kunde dock identifieras utifrån de kontinuerliga processparametrar som övervakades och vanliga variationer i permeabilitet samt effekten av membranrengöring.Eftersom skumbildning är ett vanligt fenomen i MBR-anläggningar genomfördes tester med ett skumdämpande medel som doserades i pulser och kontinuerligt till den biologiska behandlingen under perioden med kraftig skumbildning (mars-juni). Även om skumning inte upphörde helt så kunde en god minskning och kontroll av skumning uppnås. En optimal effekt konstaterades vid en kontinuerlig dos på > 10 ppm. Men även om produkten har visat sig ha en positiv effekt på skumning i MBR-piloten, framstår inte en permanent användning i fullskala som ekonomiskt genomförbar på grund av den höga förbrukningen.Tester med reducerat RAS-flöde från 4×Qin enligt design till 2×Qin syftade till att minska energiförbrukningen. Ett minskat RAS-flöde skulle dock innebära en ökad slamkoncentration i membrantankarna, vilket kan ha negativa effekter på membranets prestanda med mer igensättning, vilket i sin tur kan leda till ökad luftning för membranrengöring och behov av tätare membrantvättar. Projektgruppen kunde dock inte observera några negativa effekter av det minskade RAS-flödet på membranets prestanda.Under 2021 genomfördes tester med övergång från mesofil till termofil rötning, avvattning av rötslam efter mesofil och termofil rötning, samt termofil rötning vid hög organisk belastning (OLR) och låg hydraulisk uppehållstid (HRT) i slampiloten. Resultat visar att övergången från mesofil till termofil rötning kan ske utan större problem om den organiska belastningen minskades lite vid den mest kritiska temperaturen och att stabil drift uppnåddes efter 10-12 dagar. Att utvärdera avvattningen av mesofilt och termofilt rötat slam var svårare och inga tydliga skillnader kunde observeras. En slutsats var dock att de metoder som användes för att bestämma avvattningsbarhet eller optimal polymerdos inte framstår som tillförlitliga. Försök med hög organisk belastning vid termofil rötning visade att rötkammarens prestanda kunde bibehållas upp till en OLR på cirka 4 kg VS/m3, d och en HRT på 12 d. När belastningen ökades ytterligare och HRT minskade, minskade prestandan vad gäller utrötningsgrad och biogas-/metanproduktion, även om själva reaktordriften fortfarande var stabil.Den totala resursåtgången i piloten visade att konsumtionen av glycerol var densamma som för den framtida Henriksdalsdesignen, även om kvävebelastningen i piloten var 21 % högre och den genomsnittliga totala kvävekoncentrationen i utgående vatten var med 3,9 mg TN/L lägre än design på 6 mg TN/L. Järn-/metallförbrukningen var också 73 % av den framtida Henriksdalsdesignen, även om fosforbelastningen till piloten var cirka 50 % högre jämfört med designvärden och utgående fosfatkoncentrationerna låg under målkoncentrationen. Detta förklaras främst av EBPR-aktiviteten i pilotprojektet. Dessutom var förbrukningen av rengöringskemikalier lägre än den framtida Henriksdalsdesignen även om inflödet till piloten var 30 % högre än designen.
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24.
  • Andersson, Sofia Lovisa, et al. (author)
  • MBR-tekniken  − utmaningar och möjligheter för svenska avloppsreningsverk : Praktiska erfarenheter och framtidsutsikter baserat på nio år avpilotverksamhetoch en fullskaleimplementering
  • 2023
  • Reports (other academic/artistic)abstract
    • Under nio år (2013–2022) har membranbioreaktorteknik (MBR) för rening av avloppsvatten utvärderats i pilotförsök vid FoUanläggningen på Hammarby Sjöstadsverk i Stockholm − inför fullskaleimplementering vid Henriksdals avloppsreningsverk där en av sju fullskalelinjer är i drift sedan 2021. Rapporten sammanfattar erfarenheter, utmaningar och möjligheter med tekniken. Membranen i Henriksdals reningsverk ska ersätta slutsteget i den konventionella aktivslamprocessen. Slammet avskiljs med filtrering genom membran med mycket små porer. Totalt kommer 1,6 miljoner m2 membranyta att installeras vilket kommer att ge fördubblad kapacitet i befintliga bassänger. Många svenska VA-organisationer behöver mer kompakta reningsverk, och flera kommuner utreder därför möjligheten att införa MBR, som blir ett allt mer konkurrenskraftigt alternativ när reningskraven höjs. I MBR-piloten renades kväve biologiskt med för- och efterdenitrifikation till mycket låga halter, <5 mg/l, vilket krävt tillsats av extern kolkälla (sju olika testades). Fosfor avskildes till som lägst 0,05 mg/l genom kemisk fällning i tre punkter med metallsalter (tre olika testades). Reningen var stabil även vid hög belastning och låga temperaturer, och utgående föroreningshalter låg under de framtida utsläppskraven på 6 mg/l kväve och 0,20 mg/l fosfor, samtidigt som förbrukningen av processkemikalier var lägre än förväntat. Biologisk fosforrening uppstod oväntat i processen; detta har dock inte noterats ännu i fullskalelinjen. Membrandriften i piloten har varit stabil. Permeabiliteten, genomsläppligheten,  var mycket god och låg mellan 600 och 200 lmh/bar. Ingen negativ inverkan av de  olika process kemikalierna kunde påvisas på membranen, utom vid extremt hög dosering av järn. Till utmaningarna med MBR-tekniken hör hög resursförbrukning då membranen rengörs med luftning och kemikalier, och återcirkulationen av slam är hög. Optimering av resursanvändningen har därför varit i fokus och bland annat resulterat i 60 % minskning av kemikaliebehovet för membranrengöring samt visat att återcirkulationen av slam kunde minskas utan att membranen stördes. En annan utmaning är ansamling av flytslam/skum i det biologiska reningssteget vilket till viss del kunde stävjas med dosering av en skumdämpande produkt, även om tekniska lösningar för avlägsnande av flytslam främst rekommenderas. En nyckel till den stabila driften och den minskade resursförbrukningen är utvecklingen av styrstrategier för biologisk och kemisk rening samt styrning av membranen. Delar av styrningen användes senare i fullskalelinjen där även membranrengöringen minskats baserat på pilotens resultat. En kartläggning visade att MBR-tekniken inte gav bättre avskiljning av mikroföroreningar och PFAS än konventionella aktivslamprocesser. Däremot visade tester att ozon och aktivt kol är mer effektivt på vatten som renats i MBR då det är helt partikelfritt. MBR-piloten har också använts för att mäta växthusgasutsläpp samt utsläpp av klorerade föroreningar i vatten och gasform, test av en membranförbättrande flux- enhancer, och för att visa hur MBR kan underlätta återanvändning av renat avloppsvatten. Rapporten avslutas med diskussion om hantering av uttjänta membran, nyttan av pilotförsök samt framtida utvecklingspotential och utmaningar för MBR-tekniken. Rapportens innehåll och resultat presenteras i korthet i början av rapporten.
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25.
  • Andersson, Simon, 1980- (author)
  • Skälig misstanke
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • This doctoral dissertation studies the legal standard of proof called reasonable suspicion (skälig misstanke). This standard is central for criminal investigations as the majority of state criminal procedural actions (tvångsmedel) are tied to it, as well as the majority of a suspect’s rights. Despite the central role played by this standard, it has not to any significant extent been researched previously. What the standard entails cannot be seen from either the law or legislative history, and there are no published cases discussing it. As the meaning of the standard is not clear, there is much room for discretion in assessments as to whether the standard has been met. There consequently is a need to clarify what reasonable suspicion entails. What is required to fulfill the standard? How is reasonable suspicion to be assessed? These questions are answered in this dissertation.My investigation demonstrates that reasonable suspicion is a three-pronged standard:A requirement of preponderance of the evidenceReasonable suspicion entails a requirement of a preponderance of the evidence (sannolikhetsövervikt). This means, somewhat simplified, that it should be more probable that the suspect is guilty than innocent. The hypothesis underlying the reasonable suspicion of alleged guilt (gärningshypotesen) should be more probable than all other plausible hypotheses combined.A requirement of individualizationThe evidence must be sufficiently individualized in order to reach the level of reasonable suspicion. The requirement of individualization is in place to prevent that persons are suspected on the basis of group membership. The same is true with respect to persons belonging to groups where the probability of crime is generally high. In such situations, there must be a concrete circumstance pointing to just that person committing a certain crime. It can be, however, circumstances having very low evidentiary value. Group membership can still be of significance with respect to the suspect, but reasonable suspicion cannot be solely based on group membership. A generally applicable concept as to that distinguishing the general from the individual cannot however be articulated. All evidentiary evaluations are in some form based on generalizations. Consequently, the issue of whether the evidence is sufficiently individualized must be assessed from case to case. The main premise is that suspicion cannot be solely based on group belonging. This is a legal-political requirement. Legal-political aspects consequently must also be taken into consideration when evaluating evidence.A requirement of robustnessEven in cases where the evidence is evaluated so that a preponderance of the evidence exists and is sufficiently individualized, the evidence still needs to be sufficiently robust. Robustness is a measure of whether good grounds exist for the conclusion. It is not a question of how ”strong” the evidence is, but rather how thoroughly the situation has been investigated. Somewhat simplified, it is a question of ”how much” evidence exists rather than the strength of the individual pieces of evidence. This requirement of robustness varies depending upon time in that it is very low at the commencement of an investigation, but as time goes by, higher requirements are placed as to the ”completeness” of the investigation.
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26.
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27.
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28.
  • Ansari, Daniel, et al. (author)
  • Pancreatic cancer : Yesterday, today and tomorrow
  • 2016
  • In: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 12:16, s. 1929-1946
  • Journal article (peer-reviewed)abstract
    • Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.
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29.
  • Bauer, Ricarda M., et al. (author)
  • Coupling of α1-adrenoceptors to ERK1/2 in the human prostate
  • 2011
  • In: Urologia internationalis. - : S. Karger AG. - 0042-1138 .- 1423-0399. ; 86:4, s. 427-433
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: α1-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α1-adrenoceptor functions besides contraction. Here, we investigated whether α1-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). METHODS: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. RESULTS: Stimulation of human prostate tissue with noradrenaline (30 μM) or phenylephrine (10 μM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 μM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. CONCLUSIONS: α1-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α1-adrenoceptors in the regulation of prostate growth.
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30.
  • Berggren, Christian, 1950-, et al. (author)
  • Projekt utan partnerskap : om kunder konsulter och leverantörer i stora engångsprojekt
  • 2001. - 1
  • In: Projekt: Organisation för målorientering och lärande. - Lund : Studentlitteratur. - 9144012438 - 9789144012438 ; , s. 202-219
  • Book chapter (other academic/artistic)abstract
    •    Svenska industriföretag, tjänsteföretag och offentliga organisationer väljer i allt högre utsträckning att bedriva verksamhet i projektform. Projektet som arbetsform har gått från att ha varit något av en undantagslösning för unika insatser till att idag framstå som en ”grundbult” i sättet att organisera stora delar av verksamheten inom företag och organisationer. Därmed har också behovet av kunskaper om projektstyrning och projektorganisation ökat dramatiskt. I denna bok behandlas ledning, organisering och lärande i olika typer av projekt. Genom att boken tydligt tar sin utgångspunkt i konkreta fallbeskrivningar och kopplar dessa till aktuell organisations- och projektforskning, lämpar den sig som lärobok på projekt- och organisationskurser inom ekonom-, ingenjörs-, civilingenjörs- och systemvetarutbildningar vid universitet och högskolor. Den är också väl lämpad att användas som kursbok i företagsintern vidareutbildning, och på universitetens externa kurser och ledarskapsprogram. Boken är även intressant för var och en som på egen hand vill fundera över projektorganisationens för- och nackdelar.
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31.
  • Bergström, Jan, 1976-, et al. (author)
  • Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting : a randomised trial
  • 2010
  • In: BMC Psychiatry. - : BioMed Central Ltd. - 1471-244X. ; 10:54
  • Journal article (peer-reviewed)abstract
    • Background: Internet administered cognitive behaviour therapy (CBT) is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internetand group administered CBT for panic disorder (with or without agoraphobia) in a randomised trial within a regular psychiatric care setting. The second aim of the study was to establish the cost-effectiveness of these interventions. Methods: Patients referred for treatment by their physician, or self-referred, were telephone-screened by a psychiatric nurse. Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist. A total of 113 consecutive patients were then randomly assigned to 10 weeks of either guided Internet delivered CBT (n = 53) or group CBT (n = 60). After treatment, and at a 6-month follow-up, patients were again assessed by the psychiatrist, blind to treatment condition. Results: Immediately after randomization 9 patients dropped out, leaving 104 patients who started treatment. Patients in both treatment conditions showed  significant improvement on the main outcome measure, the Panic Disorder Severity Scale (PDSS) after treatment. For the Internet treatment the within-group effect size (pre-post) on the PDSS was Cohen's d = 1.73, and for the group treatment it was d = 1.63. Between group effect sizes were low and treatment effects were maintained at 6-months follow-up. We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data. Group CBT utilised considerably more therapist time than did Internet CBT. Defining effect as proportion of PDSS responders, the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost-effectiveness ratios in relation to group treatment both at post-treatment and follow-up. Conclusions: This study provides support for the effectiveness of Internet CBT in a psychiatric setting for patients with panic disorder, and suggests that it is equally effective as the more widely used group administered CBT in reducing panic-and agoraphobic symptoms, as well as being more cost effective with respect to therapist time.
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32.
  • Blind, Per-Jonas, et al. (author)
  • Fast-Track Program for Liver Resection - Factors Prolonging Length of Stay
  • 2014
  • In: Hepato-Gastroenterology. - 0172-6390. ; 61:136, s. 2340-2344
  • Journal article (peer-reviewed)abstract
    • Background/Aims: Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections, factors influencing LOS within a fast-track program have been studied only to a limited extent, which was the aim of the present study. Methodology: The present study comprises the first 64 patients included in a fast-track program for liver resections introduced in March 2012. Patient outcomes were compared to a historical cohort of patients (n=62) operated in 2009. Factors prolonging LOS was analyzed by uni- and multivariate analysis. Results: Median LOS was 6 days (range 3-42 days) within the fast-track program as compared with 8 days (range 5-47 days) in the historical cohort (P=0.004). On multivariate analysis, factors increasing LOS in the fast-track group were found to be the presence of complication (P=0.018), extent of resection (major as compared to minor) (P=0.001) and inability to drink > 1250 ml on the day after surgery (P=0.002). Conclusion: Patients who can only drink limited amounts of fluid the day after-liver resection represent a subset of patients that should be given special attention within a fast-track program.
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33.
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34.
  • Chang, Ya-Ting, et al. (author)
  • Versican accumulates in vascular lesions in pulmonary arterial hypertension
  • 2016
  • In: PULMONARY CIRCULATION. - : Wiley. - 2045-8932 .- 2045-8940. ; 6:3, s. 347-359
  • Journal article (peer-reviewed)abstract
    • Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [S-35] sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
  •  
35.
  • Danielsson, Christian, et al. (author)
  • Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
  • 2013
  • In: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
  • Journal article (peer-reviewed)abstract
    • Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
  •  
36.
  • El Alaoui, Samir, et al. (author)
  • Effectiveness of Internet-Based Cognitive-Behavior Therapy for Social Anxiety Disorder in Clinical Psychiatry
  • 2015
  • In: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 83:5, s. 902-914
  • Journal article (peer-reviewed)abstract
    • Objective: Internet-based cognitive-behavioral therapy (ICBT) has received increased attention as an innovative approach to improve access to evidence-based psychological treatments. Although the efficacy of ICBT for social anxiety disorder has been established in several studies, there is limited knowledge of its effectiveness and application in clinical psychiatric care. The purpose of this study was to evaluate the effectiveness of ICBT in the treatment of social anxiety disorder and to determine the significance of patient adherence and the clinic's years of experience in delivering ICBT. Method: A longitudinal cohort study was conducted using latent growth curve modeling of patients (N = 654) treated with ICBT at an outpatient psychiatric clinic between 2009 and 2013. The primary outcome measure was the Liebowitz Social Anxiety Scale-Self-Rated. Results: Significant reductions in symptoms of social anxiety were observed after treatment (effect size d = 0.86, 99% CI [0.74, 0.98]). Improvements were sustained at 6-month follow-up (d = 1.15, 99% CI [0.99, 1.32]). Patient adherence had a positive effect on the rate of improvement. A positive association between the clinic's years of experience with ICBT and treatment outcome was also observed. Conclusions: This study suggests that ICBT for social anxiety disorder is effective when delivered within the context of a unit specialized in Internet-based psychiatric care and may be considered as a treatment alternative for implementation within the mental health care system.
  •  
37.
  • El Alaoui, Samir, et al. (author)
  • Predictors and Moderators of Internet- and Group-Based Cognitive Behaviour Therapy for Panic Disorder
  • 2013
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
  • Journal article (peer-reviewed)abstract
    • Internet-based cognitive behaviour therapy (ICBT) can be equally effective as traditional face-to-face cognitive behaviour therapy (CBT) for treating panic disorder (PD). However, little is known about the predictors and moderators of outcome of ICBT when delivered in psychiatric outpatient settings. This study investigated a selection of outcome predictors and moderators of ICBT for panic disorder based on data from a randomised controlled trial where therapist-guided ICBT was compared with group CBT (GCBT) for panic disorder. Participants (N = 104) received 10 weeks of ICBT or GCBT and were assessed before and after treatment, and after six months. Multiple regression analyses were used to test for significant predictors of treatment outcome. Predictors of positive treatment response for both modalities were having low levels of symptom severity and work impairment. In addition, anxiety sensitivity was found to have a small negative relationship with treatment outcome, suggesting that anxiety sensitivity may slightly enhance treatment response. Treatment modality had a moderating effect on the relationship between domestic impairment and outcome and on the relationship between initial age of onset of panic symptoms and treatment outcome, favouring ICBT for patients having had an early onset of PD symptoms and for patients having a high domestic functional impairment. These results suggest that both ICBT and GCBT are effective treatment modalities for PD and that it is possible to predict a significant proportion of the long-term outcome variance based on clinical variables.
  •  
38.
  • El Alaoui, Samir, et al. (author)
  • Predictors of Symptomatic Change and Adherence in Internet-Based Cognitive Behaviour Therapy for Social Anxiety Disorder in Routine Psychiatric Care
  • 2015
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
  • Journal article (peer-reviewed)abstract
    • Objective A central goal of health care is to improve patient outcomes. Although several studies have demonstrated the effectiveness of therapist guided internet-based cognitive behaviour therapy (ICBT) for social anxiety disorder (SAD), a significant proportion of patients do not respond to treatment. Consequently, the aim of this study was to identify individual characteristics and treatment program related factors that could help clinicians predict treatment outcomes and adherence for individuals with SAD. Method The sample comprised longitudinal data collected during a 4-year period of adult individuals (N = 764) treated for SAD at a public service psychiatric clinic. Weekly self-rated Liebowitz Social Anxiety Scale (LSAS-SR) scores were provided. Rates of symptomatic change during treatment and adherence levels were analysed using multilevel modelling. The following domains of prognostic variables were examined: (a) socio-demographic variables; (b) clinical characteristics; (c) family history of mental illness; and (d) treatment-related factors. Results Higher treatment credibility and adherence predicted a faster rate of improvement during treatment, whereas higher overall functioning level evidenced a slower rate of improvement. Treatment credibility was the strongest predictor of greater adherence. Having a family history of SAD-like symptoms was also associated with greater adherence, whereas Attention-Deficit/Hyperactivity Disorder (ADHD)-like symptoms, male gender, and family history of minor depression predicted lower adherence. Also, the amount of therapist time spent per treatment module was negatively associated with adherence. Conclusions Results from a large clinical sample indicate that the credibility of ICBT is the strongest prognostic factor explaining individual differences in both adherence level and symptomatic improvement. Early screening of ADHD-like symptoms may help clinicians identify patients who might need extra support or an adjusted treatment. Therapist behaviours that promote adherence may be important for treatment response, although more research is needed in order to determine what type of support would be most beneficial.
  •  
39.
  • Enander, Jesper, et al. (author)
  • Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial
  • 2016
  • In: BMJ-BRITISH MEDICAL JOURNAL. - : BMJ PUBLISHING GROUP. - 1756-1833. ; 352:i241
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. DESIGN A 12 week single blind parallel group randomised controlled trial. SETTING Academic medical centre. PARTICIPANTS 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of >= 20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. INTERVENTIONS Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. MAIN OUTCOME MEASURES The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a >= 30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. RESULTS BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference -7.1 points, 95% confidence interval -9.8 to -4.4), depression (MADRS-S group difference -4.5 points, -7.5 to -1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self reported satisfaction was high. CONCLUSIONS CBT can be delivered safely via the internet to patients with body dysmorphic disorder. BDD-NET has the potential to increase access to evidence based psychiatric care for this mental disorder, in line with NICE priority recommendations. It could be particularly useful in a stepped care approach, in which general practitioner or other mental health professionals can offer treatment to people with mild to moderate symptoms at low risk of suicide.
  •  
40.
  • Fuellhase, Claudius, et al. (author)
  • Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats
  • 2013
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 189:6, s. 2364-2370
  • Journal article (peer-reviewed)abstract
    • Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.
  •  
41.
  • Gallardo-Dodd, Carlos J., et al. (author)
  • Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells
  • 2023
  • In: Science Advances. - 2375-2548. ; 9:34
  • Journal article (peer-reviewed)abstract
    • The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers. Samples were collected 7 days before DI, at day 7, 14, and 21 during DI, and 7 days after DI. RNA sequencing of CD3(+) T cells revealed transcriptional alterations across all time points, with most changes occurring 14 days after DI exposure. At day 21, T cells showed evidence of adaptation with a transcriptional profile resembling that of 7 days before DI. At 7 days after DI, T cells again changed their transcriptional profile. These data suggest that T cells adapt by rewiring their transcriptomes in response to simulated weightlessness and that remodeling cues persist when reexposed to normal gravity.
  •  
42.
  • George, Zandra, 1985, et al. (author)
  • Two-in-one : Cathode modification and improved solar cell blend stability through addition of modified fullerenes
  • 2016
  • In: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 4:7, s. 2663-2669
  • Journal article (peer-reviewed)abstract
    • The synthesis of dual purpose modified fullerenes with pyridine-as well as amine-functional groups is reported. Addition of these fullerenes to a polymer : fullerene bulk-heterojunction blend based on a thiophene-quinoxaline donor polymer is found to modify the active layer/cathode interface of inverted solar cells (glass/ITO/active layer/MoO3/Al). In particular the open-circuit voltage of devices is increased from 0.1 V to about 0.7 V, which results in a drastic rise in photovoltaic performance with a power conversion efficiency of up to 3%. At the same time, presence of the functionalised fullerene additives prevents the detrimental formation of micrometre-sized fullerene crystals upon annealing at 140 degrees C. As a result, the device performance is retained, which promises significantly increased thermal stability of the bulk-heterojunction blend nanostructure.
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43.
  • Ghosheh, Nidal, 1975-, et al. (author)
  • Human Pluripotent Stem Cell-Derived Hepatocytes Show Higher Transcriptional Correlation with Adult Liver Tissue than with Fetal Liver Tissue
  • 2020
  • In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:10, s. 4816-4827
  • Journal article (peer-reviewed)abstract
    • Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 
  •  
44.
  • Gratzke, Christian, et al. (author)
  • Cannabinor, a Selective Cannabinoid-2 Receptor Agonist, Improves Bladder Emptying in Rats With Partial Urethral Obstruction
  • 2011
  • In: JOURNAL OF UROLOGY. - : Elsevier Science B.V. Amsterdam. - 0022-5347 .- 1527-3792. ; 185:2, s. 731-736
  • Journal article (peer-reviewed)abstract
    • Purpose: We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter andamp; Gamble Pharmaceuticals, Cincinnatti, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle. Materials and Methods: A total of 24 female Sprague-Dawley(R) rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies. Results: Mean +/- SEM bladder weight was 0.97 +/- 0.15 gm in controls and 0.53 +/- 0.08 gm in cannabinor treated rats (p andlt; 0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 +/- 0.07 and 0.06 +/- 0.02 ml, mean micturition compliance was 0.032 +/- 0.006 and 0.069 +/- 0.016 ml/cm H2O, and mean bladder wall force at the start of flow was 950 +/- 280 and 1,647 +/- 325 mN/gm, respectively (each p andlt; 0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma(R)) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips. Conclusions: In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction.
  •  
45.
  • Gratzke, Christian, et al. (author)
  • Distribution and Function of Cannabinoid Receptors 1 and 2 in the Rat, Monkey and Human Bladder
  • 2009
  • In: JOURNAL OF UROLOGY. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 181:4, s. 1939-1948
  • Journal article (peer-reviewed)abstract
    • Purpose: We investigated the distribution of cannabinoid receptor subtypes 1 and 2 in the detrusor of different species and studied the effects of cannabinoid receptor 1 and 2 agonists on bladder function. Materials and Methods: Cannabinoid receptor 1 and 2 expression was studied with Western blot and immunohistochemistry in rat, monkey and human detrusors. Co-staining was done for markers of sensory nerves using calcitonin gene-related peptide (Euro-Diagnostica, Malmo, Sweden) and transient receptor potential vanilloid 1, and for cholinergic nerves using VAChT (Santa Cruz Biotechnology, Santa Cruz, California). Actions of the endogenous cannabinoid receptor-1 and 2 agonist anandamide (Sigma (R)), and the cannabinoid receptor 1 and 2 agonist CP55,940 (Sigma) on isolated detrusor and during cystometry in conscious rats were recorded. Results: Higher expression of cannabinoid receptor 2 but not cannabinoid receptor 1 was noted in the mucosa than in the detrusor. Compared to the detrusor larger amounts of cannabinoid receptor 2 containing nerves that also expressed transient receptor potential vanilloid 1 or calcitonin gene-related peptide were observed in the suburothelium. Nerve fibers containing cannabinoid receptor 2 and VAChT were located in the detrusor. Neither anandamide nor CP55,940 affected isolated detrusor carbachol (Sigma) contractions. Nerve contractions were enhanced by 10 mu M anandamide and decreased by 10 AM CP55,940 (P<0.05). In vivo CP55,940 increased the micturition interval by 46% and threshold pressure by 124% (p <0.05). Anandamide increased threshold pressure by 26% and decreased the micturition interval by 19% (p <0.05 and <0.01, respectively). Conclusions: The distribution of cannabinoid receptor 2 on sensory nerves and in the urothelium, and effects by CP55940 on the micturition interval and threshold pressure suggest a role for cannabinoid receptor 2 in bladder afferent signals. Co-expression of VAChT and cannabinoid receptor 2, and effects by CP55940 on nerve contractions suggest a cannabinoid receptor 2 mediated modulatory effect on cholinergic nerve activity. Anandamide may not be a good tool for cannabinoid receptor studies due to its activity at other receptors.
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46.
  • Gratzke, Christian, et al. (author)
  • Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats
  • 2010
  • In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 57:6, s. 1093-1100
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established.OBJECTIVES: Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function.DESIGN, SETTING, AND PARTICIPANTS: Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated.MEASUREMENTS: Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used.RESULTS AND LIMITATIONS: CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0mg/kg increased micturition intervals and volumes by 52% (p<0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively. Cannabinor 0.3 or 1.0mg/kg or vehicle did not affect urodynamic parameters.CONCLUSIONS: Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on "afferent" urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited.
  •  
47.
  • Gratzke, Christian, et al. (author)
  • Localization and Function of Cannabinoid Receptors in the Corpus Cavernosum: Basis for Modulation of Nitric Oxide Synthase Nerve Activity
  • 2010
  • In: EUROPEAN UROLOGY. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:2, s. 342-348
  • Journal article (peer-reviewed)abstract
    • Background: Anandamide, a proposed endogenous cannabinoid (CB) agonist, has been shown to enhance neurogenic responses in vitro of the rat corpus cavernosal tissue (CC). However, no information is available on the distribution of CB-receptors or effects by anandamide in CC from primates or humans. Objective: To characterize the distribution of CB-receptor isoforms in the human and primate CC and to investigate the effects of anandamide on isolated CC preparations. Design, setting, and participants: CC tissue was excised from the crura penis of six rhesus monkeys and five patients. Expression and distribution of CB1 and CB2 receptors were characterized with Western blot analyses and immunohistochemical investigations. The effects of anandamide on isolated CC preparations were analyzed during pharmacologic and nerve-mediated activation of primate tissue in aerated organ baths. Measurements: The expression and localization of CB1 and CB2 receptors in the primate CC and effects of anandamide on nerve-mediated relaxations and pharmacologically evoked contractions. Results and limitations: Western blot experiments revealed CB1 and CB2 receptors at expected band weights. Within and between strands of CC smooth muscle, CB1 and CB2 immunoreactivity (IR) was found in nerve fibers that also expressed IR for nitric oxide synthase (NOS) or transient receptor potential V1 (TRPV1). Neither CB1-IR nor CB2-IR nerves were colocalized with calcitoningene-related peptide (CGRP)-containing or tyrosine hydroxylase-containing nerves. No differences were observed between primate and human CC sections. Anandamide (10(-9) to 10(-4) M) had no contractile effects on CC smooth muscle, no relaxant effects on precontracted preparations, and no effect on phenylephrine-induced contractions. However, anandamide (10 mu M) inhibited electrically evoked smooth-muscle relaxations (34-48%; p andlt;= 0.05). Conclusions: CB1 and CB2 receptors are located on NOS-containing nerves in primate and human CC tissue. In contrast to findings in rats, anandamide antagonized nerve-mediated relaxations of the primate CC, suggesting important species differences for CB-mediated functions. The results also suggest a peripheral mechanism for cannabis-related sexual dysfunction.
  •  
48.
  • Gratzke, Christian, et al. (author)
  • Transient Receptor Potential A1 and Cannabinoid Receptor Activity in Human Normal and Hyperplastic Prostate: Relation to Nerves and Interstitial Cells
  • 2010
  • In: EUROPEAN UROLOGY. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:5, s. 902-910
  • Journal article (peer-reviewed)abstract
    • Background: Ion channel transient receptor potential A1 (TRPA1) and cannabinoid (CB) receptors are involved in mechanoafferent signaling from the bladder and the urethra. Objective: To characterize TRPA1-, CB1-, and CB2-receptor activities in the human prostate. Design, setting, and participants: Prostate specimens were obtained from 12 patients undergoing radical prostatectomy. We studied expressions (n = 6) of TRPA1, CB1, and CB2 receptors and effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and CP 55940 (a CB1/CB2 agonist) on prostatic preparations. Measurements: Western blot, immunohistochemistry, and functional experiments were performed. Results and limitations: Western blot detected expected bands for CB1, CB2, and TRPA1. TRPA1 immunoreactivity was located on nerves that were positive for CB1, CB2, calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), or vesicular acetylcholine transporter (VAChT). CB1 and CB2 immunoreactivity was found on nerves that were positive for NOS, VAChT, or CGRP. Adrenergic nerves were not immunoreactive for TRPA1, CB1, or CB2. In nodular hyperplasia, nerves containing the above markers were scarce or absent. TRPA1 immunoreactivity was detected in cyclic guanosinemonophosphate-positive basal cells of the glandular epithelium. Basal or subepithelial TRPA1-immunoreactive cells contained vimentin and c-kit immunoreactivity. CA and NaHS relaxed precontracted preparations by 55 +/- 7% and 35 +/- 3% (n = 6 for each). CP 55940, NaHS, AI, capsaicin, and CA decreased nerve contractions up to 27%, 80%, 47%, and 87%, respectively (n = 6 for each). Conclusions: The distribution and function of TRPA1 and CB receptors in prostatic tissue suggest a role for these receptors in mechanoafferent signals, epithelial homeostasis, emission, or inflammation of the human prostate.
  •  
49.
  • Gratzke, Christian, et al. (author)
  • Transient Receptor Potential A1 (TRPA1) Activity in the Human Urethra-Evidence for a Functional Role for TRPA1 in the Outflow Region
  • 2009
  • In: EUROPEAN UROLOGY. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 55:3, s. 696-704
  • Journal article (peer-reviewed)abstract
    • Background: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. Objectives: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. Design, settings, and participants: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. Measurements: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (A1), cinnamaldehyde (CA), and NaHS (donor of H2S) on tension of urethral strips were investigated in tissue baths. Results and limitations: TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations.´ Conclusions: The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.
  •  
50.
  • Gråsjö, Johan, et al. (author)
  • Electronic structure of water molecules confined in a micelle lattice
  • 2009
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 113:24, s. 8201-8205
  • Journal article (peer-reviewed)abstract
    • Oxygen K absorption and emission spectra of water molecules confined in dodecyltrimethyl ammonium chloride micelle structures are presented. The local electronic structure of the water molecules is found to be dramatically different from the electronic structure of water molecules in the gas-phase as well as in liquid water. Hybridization with states of the ions in the surrounding ions is directly observed, and evidence for stabilization of the water molecules relative to molecules in bulk water is found.
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Type of content
peer-reviewed (611)
other academic/artistic (159)
pop. science, debate, etc. (48)
Author/Editor
Fager, Christian, 19 ... (48)
Andersson, Mats, 196 ... (32)
Inganäs, Olle (15)
Backes, M. (14)
Berge, D. (14)
Lohse, T. (14)
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Heinzelmann, G. (14)
Tjus, J. Becker (14)
Katz, U. (14)
Casanova, S. (14)
Bulik, T. (14)
Edwards, T. (14)
Klepser, S. (14)
Bolmont, J (14)
Chen, A. (14)
Abdalla, H. (14)
Abramowski, A. (14)
Aharonian, F. (14)
Benkhali, F. Ait (14)
Akhperjanian, A. G. (14)
Arrieta, M. (14)
Aubert, P. (14)
Balzer, A. (14)
Barnard, M. (14)
Becherini, Yvonne (14)
Bernhard, S. (14)
Blackwell, R. (14)
Boisson, C. (14)
Bordas, P. (14)
Bregeon, J. (14)
Brun, F. (14)
Brun, P. (14)
Bryan, M. (14)
Capasso, M. (14)
Carr, J. (14)
Chakraborty, N. (14)
Chaves, R. C. G. (14)
Chevalier, J. (14)
Colafrancesco, S. (14)
Cologna, G. (14)
Condon, B. (14)
Cui, Y. (14)
Davids, I. D. (14)
Degrange, B. (14)
Devin, J. (14)
Domainko, W. (14)
Donath, A. (14)
Drury, L. O 'C. (14)
Dutson, K. (14)
Dyks, J. (14)
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University
Linköping University (171)
Lund University (159)
Chalmers University of Technology (159)
Uppsala University (131)
Karolinska Institutet (106)
University of Gothenburg (82)
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Linnaeus University (50)
Stockholm University (46)
Umeå University (41)
RISE (31)
Södertörn University (28)
University of Skövde (27)
Luleå University of Technology (25)
Royal Institute of Technology (23)
IVL Swedish Environmental Research Institute (17)
Örebro University (14)
Swedish University of Agricultural Sciences (14)
Jönköping University (11)
Malmö University (10)
University of Borås (7)
University West (6)
VTI - The Swedish National Road and Transport Research Institute (5)
Blekinge Institute of Technology (4)
Swedish Environmental Protection Agency (2)
Mid Sweden University (2)
Karlstad University (2)
Kristianstad University College (1)
University of Gävle (1)
Swedish Museum of Natural History (1)
Sophiahemmet University College (1)
The Royal Institute of Art (1)
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Language
English (715)
Swedish (96)
Undefined language (6)
Danish (1)
Research subject (UKÄ/SCB)
Medical and Health Sciences (237)
Natural sciences (213)
Engineering and Technology (197)
Social Sciences (138)
Humanities (10)
Agricultural Sciences (8)

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