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Sökning: WFRF:(Gerhard Karin)

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  • Rödström, Karin, 1986, et al. (författare)
  • Structural studies of staphylococcal enterotoxin H in complex with T cell receptor and major histocompatibility complex class II
  • 2010
  • Ingår i: FEBS JOURNAL. - 1742-464X. ; 2010, 277, s. 53-54
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Superantigens (SAgs) are bacterial toxins capable of cross-linking the immune receptors of the host, the T cell receptor (TCR) and major histocompatibility complex (MHC) class II, and thereby trigger a massive release of cytokines. This could lead to toxic shock syndrome, which can have a fatal outcome. Here, we present the crystal structure of the ternary complex between the superantigen, staphylococcal enterotoxin H (SEH), TCR and MHC, as well as the dimer complex, including only TCR and SEH. It is evident that SEH interacts with the variable α domain (Vα) of TCR, in sharp contrast to previously studied SAgs that interact with the Vβ domain. Due to the high structural conservation of amino acids in SEH that are crucial for the interaction, we propose that in addition to Vβ activation of T cells, there are SAgs, in addition to SEH, which are able to activate T cells through Vα as well. In addition to providing crucial information regarding the nature of TCR-mediated recognition of superantigens, the finding have central implications for future strategies aimed at preventing or modulating the often pathogenic response to superantigens.
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  • Saline, Maria, et al. (författare)
  • The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation.
  • 2010
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 1:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Superantigens (SAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (MHC) class II, conventionally through the variable β-domain of TCR (TCRVβ). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (SEH) and its human receptors, MHC class II and TCR. The structure demonstrates that SEH predominantly interacts with the variable α-domain of TCR (TCRVα), which is supported by nuclear magnetic resonance (NMR) analyses. Furthermore, there is no contact between MHC and TCR upon complex formation. Structural analyses suggest that the major contact points to TCRVα are conserved among other bacterial SAgs. Consequently, a new dimension of SAg biology emerges, suggesting that in addition to the conventional interactions with the TCRVβ domain, SAgs can also activate T cells through the TCRVα domain.
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  • Akhter, Tansim, 1967-, et al. (författare)
  • Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia
  • 2017
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 50, s. 93-99
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.
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  • Akhter, Tansim, 1967-, et al. (författare)
  • Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.
  • 2017
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 241, s. 417-422
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.
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  • Allamani, Allaman, et al. (författare)
  • Contextual Determinants of Alcohol Consumption Changes and Preventive Alcohol Policies : A 12-Country European Study in Progress 2011
  • 2011
  • Ingår i: Substance Use & Misuse. - : Informa UK Limited. - 1082-6084 .- 1532-2491. ; 46:10, s. 1288-1303
  • Tidskriftsartikel (refereegranskat)abstract
    • Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes
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  • Almlöv, Jonas, et al. (författare)
  • Therapist effects in guided internet-delivered CBT for Anxiety Disorders
  • 2011
  • Ingår i: Behavioural and Cognitive Psychotherapy. - London : Wisepress. - 1352-4658 .- 1469-1833. ; 39:3, s. 311-322
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Guided internet-delivered CBT for anxiety disorders has received increasing empirical support, but little is known regarding the role of the therapist. Aims: This study addressed therapist factors in guided internet-delivered cognitive behavioural therapy for anxiety disorders. Method: Data from three controlled trials with a total N of 119 were analyzed with attention to differences between eight therapists. Results: No significant mean level differences between therapists appeared in the dataset. However, one significant intraclass correlation between participants was found, suggesting that the outcome on the Beck Anxiety Inventory might have been influenced by the impact of the individual therapists. Conclusion: The therapist can possibly have some influence on the outcome of guided internet-delivered CBT for anxiety disorders, but studies with more statistical power are needed to establish whether therapist effects are present in this modality of psychological treatment. The present study was underpowered to detect minor therapist effects.
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  • Andersson, Gerhard, et al. (författare)
  • Free choice of treatment content, support on demand and supervision in internet-delivered CBT for adults with depression : A randomized factorial design trial
  • 2023
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 162
  • Tidskriftsartikel (refereegranskat)abstract
    • Even if much is known regarding the effects of internet-delivered cognitive behaviour therapy (ICBT) for depression there are several topics that have not been studied. In this factorial design trial with 197 participants we investigated if clients in ICBT could select treatment modules themselves based on a selection of 15 tailored treatment modules developed for use in ICBT for depression. We contrasted this against clinician-tailored module selection. We also investigated if support on demand (initiated by the client) could work as well as scheduled support. Finally, we tested if clients that were mentioned in supervision would improve more than clients not mentioned (with the exception of acute cases). The treatment period lasted for 10 weeks, and we measured effects at post-treatment and two-year follow-up. Measures of depression and secondary outcomes were collected at pre-treatment, post-treatment and two-year follow-up. Overall, within-group effects were large across con-ditions (e.g., d = 1.73 on the BDI-II). We also found a small but significant difference in favour of self-tailored treatment over clinician-tailored (d = 0.26). Within-group effects for the secondary measures were all moderate to large including a test of knowledge about CBT. The other two contrasts "support on demand" and "supervision" yielded mostly non-significant differences, with the exception of a larger dropout rate in the support on demand condition. There were few negative effects (2.2%). Effects were largely maintained at a two-year follow-up. We conclude that clients can choose treatment modules and that support on demand may work. The role of su-pervision is not yet clear as advice can be transferred across clients.
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  • Bargoria, Victor, et al. (författare)
  • Running for your life : A qualitative study of champion long-distance runners strategies to sustain excellence in performance and health
  • 2020
  • Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 23:8, s. 715-720
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo investigate champion long-distance runners’ strategies for managing injury and illness symptoms and staying well.DesignQualitative research study.MethodsTwelve long-distance runners were interviewed immediately after having competed in World Championships finals. Thematic analysis was used to categorise and structure the data. The results were presented as primary themes and overarching constructs representing connections between the primary themes.ResultsThe champion runners’ basic tactic to manage symptoms of ill health was characterized by rapid adjustment of sports load and a strong incentive to learn from experience and professional advice. This tactic was named here educated flexibility. A secondary exigency tactic was associated with reaching short-term goals and a consequential acceptance of health hazards. The runners used economic and other environmental strain to explain use of the exigency tactic. Most champion runners’ long-term strategy to stay well included both tactics successfully combined to maintain a performance level assuring a regular income. Avoidance of letting environmental strain and health problems create vicious circles was at the centre of these strategies.ConclusionsChampion runners’ main strategy to stay well and sustain their superiority in performance was characterized by constantly paying attention to symptoms of ill health, listening to medical advice, and not letting environmental strain interfere with adjustment of sports load. Many top-level runners originate from global regions where formal education programs and health insurance plans are poorly regulated and supported. Bio-psychosocial models including empowerment at individual and systems levels should be considered when health services are planned for professional runners.
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  • Bas-Hoogendam, Janna Marie, et al. (författare)
  • Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
  • 2017
  • Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
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  • Bendelin, Nina, et al. (författare)
  • Experiences of guided Internet-based cognitive-behavioural treatment for depression : A qualitative study
  • 2011
  • Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 11:107
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Internet-based self-help treatment with minimal therapist contact has been shown to have an effect in treating various conditions. The objective of this study was to explore participants’ views of Internet administrated guided self-help treatment for depression. Methods: In-depth interviews were conducted with 12 strategically selected participants and qualitative methods with components of both thematic analysis and grounded theory were used in the analyses. Results: Three distinct change processes relating to how participants worked with the treatment material emerged which were categorized as (a) Readers, (b) Strivers, and (c) Doers. These processes dealt with attitudes towards treatment, views on motivational aspects of the treatment, and perceptions of consequences of the treatment. Conclusions: We conclude that the findings correspond with existing theoretical models of face-to-face psychotherapy within qualitative process research. Persons who take responsibility for the treatment and also attribute success to themselves appear to benefit more. Motivation is a crucial aspect of guided self-help in the treatment of depression.
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  • Bendelin, Nina, et al. (författare)
  • Patients' experiences of internet-based Acceptance and commitment therapy for chronic pain : a qualitative study
  • 2020
  • Ingår i: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic pain is a globally widespread condition with complex clusters of symptoms within a heterogeneous patient group. Internet-delivered Acceptance and Commitment Therapy (IACT) has shown promising results in the treatment of chronic pain. How IACT is experienced by patients is less well known. Qualitative studies of patients' experiences are needed to further understand factors behind both engagement and negative effects. The aim of this study was to explore how IACT was experienced by chronic pain patients who had participated in a controlled trial.Methods: Through an open and exploratory approach this study aimed to investigate how IACT was experienced when delivered as a guided self-help program to persons with chronic pain. Eleven participants were interviewed over telephone after completing IACT.Results: Qualitative analysis based on grounded theory resulted in 2 core categories and 8 subcategories. In treatment: Physical and cognitive restraints, Time and deadline, Therapist contact, and Self-confrontation. After treatment: Attitude to pain, Image of pain, Control or Command, and Acting with pain. Individual differences as well as specific conditions of the treatment may explain variations in how the treatment was approached, experienced and what consequences it led to. Therapist guidance and deadlines for homework play complex roles in relation to autonomy and change.Conclusions: Adjusting treatment content and format based on participants' characteristics, such as expectations, motivation and restraints, might positively affect engagement, autonomy and change. Further research on attrition and negative effects of treatment might clarify what enables chronic pain patients to benefit from IACT.
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  • Berg, Ida, et al. (författare)
  • “Good job!” : Therapists' encouragement, affirmation, and personal address in internet-based cognitive behavior therapy for adolescents with depression
  • 2022
  • Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 30
  • Tidskriftsartikel (refereegranskat)abstract
    • Internet-delivered interventions are generally effective for psychological problems. While the presence of a clinician guiding the client via text messages typically leads to better outcomes, the characteristics of what constitutes high-quality communication are less well investigated. This study aimed to identify how an internet therapist most effectively communicates with clients in internet-delivered cognitive behavioral therapy (ICBT). Using data from a treatment study of depressed adolescents with a focus on participants who had a positive outcome, messages from therapists were analyzed using thematic analysis. The study focused on the therapist's 1) encouragement and 2) affirmation, and how the therapists used 3) personal address. The analysis resulted in a total of twelve themes (Persistence Wins, You Are a Superhero, You Make Your Luck, You Understand, Hard Times, You Are Like Others, My View on the Matter, Time for a Change, Welcome In, Let Me Help You, You Affect Me, and I Am Human). Overall, the themes form patterns where treatment is described as hard work that requires a motivated client who is encouraged by the therapist. The findings are discussed based on the cognitive behavioral theoretical foundation of the treatment, prior research on therapist behaviors, and the fact that the treatment is provided over the internet.
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  • Berg, Matilda, et al. (författare)
  • The Role of Learning Support and Chat-Sessions in Guided Internet-Based Cognitive Behavioral Therapy for Adolescents With Anxiety: A Factorial Design Study
  • 2020
  • Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Increased awareness of anxiety in adolescents emphasises the need for effective interventions. Internet-based cognitive behavioural therapy (ICBT) could be a resource-effective and evidence-based treatment option, but little is known about how to optimize ICBT or which factors boost outcomes. Recently, the role of knowledge in psychotherapy has received increased focus. Further, chat-sessions are of interest when trying to optimize ICBT for youths. This study aimed to evaluate the role of learning support and chat-sessions during ICBT for adolescent anxiety, using a factorial design. Method A total of 120 adolescents were randomised to one of four treatment groups, in a 2x2 design with two factors: with or without learning support and/or chat-sessions. Results Anxiety and depressive symptoms were reduced (Beck Anxiety Inventory- BAI; Cohensd=0.72; Beck Depression Inventory- BDI;d=0.97). There was a main effect of learning support on BAI (d=0.38), and learning support increased knowledge gain (d =0.42). There were no main effects or interactions related to the chat-sessions. Treatment effects were maintained at 6-months, but the added effect of learning support had by then vanished. Conclusion ICBT can be an effective alternative when treating adolescents with anxiety. Learning support could be of importance to enhance short-term treatment effects, and should be investigated further.
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  • Berman, Anne H., Professor, et al. (författare)
  • Transdiagnostic and tailored internet intervention to improve mental health among university students : Research protocol for a randomized controlled trial
  • 2024
  • Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
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  • Bonham, LW, et al. (författare)
  • Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
  • Tidskriftsartikel (refereegranskat)abstract
    • The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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  • Burman, Maria, et al. (författare)
  • Närmare varandra : Nio veckor till en starkare parrelation
  • 2018
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Relationsproblem är vanliga och påverkar oss på många plan. Denna självhjälpsbok får par att se hur problemen inte ligger hos den ena eller andra partnern utan uppstår i samspelet mellan dem. Paren guidas till att hitta mönster och ömma punkter i sitt samspel och får hjälp att bygga vidare på styrkor de har som par.
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  • Carlbring, Per, et al. (författare)
  • Adverse effects in internet-based cognitive-behavior versus psychodynamic therapy
  • 2022
  • Ingår i: EABCT 2022: Re-Thinking CBT: providing startegies for a new way of living. ; , s. 66-66
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Internet-based psychological treatments provide many benefits for patients with psychiatric disorders, but research also suggests that negative effects might occur from the interventions involved.Methods: A total of 2400 participants presenting with anxiety and/or depression were randomized into 12 subgroups (n=200 each) based on treatment modality (Cognitive Behavior Therapy vs. Psychodynamic Therapy vs. Waitlist), duration (8 vs. 16 weeks), and moderated discussion forum (Yes vs. No). In addition to weekly measurements of the primary outcome measure (PHQ-9 & GAD-7), the Negative Effects Questionnaire was administered post-treatment. The Negative Effects Questionnaire has been proposed as a valuable instrument for investigating the negative effects of psychological treatments. An exploratory factor analysis suggested a six-factor solution: symptoms (“I felt more worried”), quality (“I did not always understand my treatment”), dependency (“I think that I have developed a dependency on my treatment”), stigma (“I became afraid that other people would find out about my treatment”), hopelessness (“I started thinking that the issue I was seeking help for could not be made any better”), and failure (“I lost faith in myself”).Results: All 2400 participants have been recruited. However, all post-assessment data is not yet collected at the time of writing (but will be by the time of the conference). This talk will focus on the occurrence and characteristics of the potential negative effects of internet-based treatment in the 12 subgroups.Discussion: Negative effects of psychotherapy are multifaceted, warranting careful considerations for them to be monitored and reported in research settings and routine care.
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  • Carlbring, Per, et al. (författare)
  • Comparing Transdiagnostic Treatments: Unified Protocol vs. Affect Phobia Therapy and the Role of Negative Effects
  • 2023
  • Ingår i: Abstracts and Program Parallel Sessions. ; , s. 32-32
  • Konferensbidrag (refereegranskat)abstract
    • Aim: The aim of the TRAbee study was to compare the effectiveness of two transdiagnostic treatment modalities, Unified Protocol (Cognitive Behavior Therapy) and Affect Phobia Therapy (Psychodynamic Psychotherapy), in alleviating psychological distress and to examine the relative differences in the incidence of negative effects as assessed by the Negative Effects Questionnaire.Methods: This study is a randomized controlled trial with 2,400 participants divided into 12 subgroups based on treatment modality (CBT vs. PDT vs. waitlist), duration (8 or 16 weeks of treatment), and discussion forum access (yes/no). Participants were randomly assigned and measured weekly during treatment, and then at 6, 12, and 24 months. Inclusion criteria were: age 18 years or older, ability to read/write Swedish, access to a smartphone/computer, GAD-7 score ≥5, and/or PHQ-9 score ≥10. Exclusion criteria included: current psychological treatment, recent medication change, severe depression/suicidality. Outcome measures included the Generalized Anxiety Disorder 7-item scale (GAD-7), the Patient Health Questionnaire 9-item scale (PHQ-9), the Personality Inventory for DSM-5 (PID-5), the Reflective Functioning Questionnaire 8-item scale (RFQ- 8), the Negative Effects Questionnaire (NEQ), and the Brunnsviken Brief Quality of Life scale (BBQ).Results: Follow-up data is still being collected, but preliminary results, including 12-month follow-up, will be available at the ISRII conference. The results will report on the relative differences in the incidence of negative effects between the treatments as assessed by the NEQ scale.Conclusions: The study will provide insights into the comparative effectiveness of Unified Protocol and Affect Phobia Therapy in addressing psychological disorders in a transdiagnostic manner, as well as shedding light on the differences in negative effects experienced by patients undergoing these treatments. This information may inform future treatment approaches and help to optimize patient outcomes.
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  • Carlbring, Per, et al. (författare)
  • Lessons learned from 'TRAbee' – a large full-factorial designed study (n=2400) targeting depression and/or anxiety
  • 2022
  • Ingår i: EABCT 2022: Re-Thinking CBT: providing startegies for a new way of living. ; , s. 117-117
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Typically, internet-based treatment programs are effective for various psychological problems. However, diagnosing, and matching treatments to an individual's need, is a challenge and potentially resource-intensive. In addition, it is unknown what the optimal treatment length is and whether access to an online forum is beneficial for treatment adherence and subsequent outcome. In this study, the Iterapi platform fully automated all decisions and communication with the participants, maximizing scalability.Methods: A total of 2400 participants presenting with anxiety and/or depression were randomized into 12 subgroups (n=200 each) based on treatment modality, duration, and moderated discussion forum (Yes vs. No). Weekly measurements using PHQ9 and GAD7 were the primary outcome measures.The treatments were based on Cognitive Behavior Therapy (Unified Protocol) or Psychodynamic models and treatment principles (Affect Phobia). Both Unified Protocol and the Affect Phobia treatment program are transdiagnostic methods targeting symptoms of anxiety and depression. The participants were also randomly assigned to either having (50%) or not having (50%) access to a discussion forum that a clinician moderated. Finally, all participants of the two treatment groups and the waitlist-control group were randomly assigned to either an 8- or 16-week intervention duration.Results: All 2400 participants have been recruited. However, all post-assessment data is not yet collected at the time of writing (but will be by the time of the conference). This talk will focus on design considerations and lessons learned from the 'TRAbee' study.Discussion: Since the weekly assessment of outcome has been collected, the statistical power is strong, especially since the total number of participants is 2400. The outcome will answer several dissemination questions, including treatment length, discussion boards' added value, and treatment type (CBT vs. PDT).
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  • Carlbring, Per, et al. (författare)
  • TRAbee: Internet-delivered transdiagnostic self-help treatments for anxiety and/or depression : Preliminary results from a full-factorial designed randomized control trial
  • 2022
  • Ingår i: Abstracts from the 11th Swedish Congress on internet interventions (SWEsrii), Gothenburg, Sweden, 23-24 May 2022. - Linköping : Linköping University Electronic Press. ; , s. 14-15
  • Konferensbidrag (refereegranskat)abstract
    • Traditional evidence-based psychological treatments are often diagnosis-specific, with treatment manuals being developed for specific diagnoses. This methodology has been criticized by some for not corresponding with the clinical reality of individual variability of symptoms, comorbitity with other psychiatric diagnoses and subclinical symptoms of other conditions. A possible way of adapting treatments to clinical reality is through transdiagnostic modes of treatment.Transdiagnostic treatments have the great advantage of potentially being suitable to a larger, and likely more representative population. Within psychological treatment there are two main transdiagnostic modalities; Unified Protocol and Affect Phobia Therapy. Unified Protocol is based on Cognitive Behaviour Therapy and is directed at emotional regulation as an important maintaining, transdiagnostic factor. Affect phobia therapy has its theoretical roots in modern Psychodynamic Theory and is focused on breaking unconscious maladaptive patterns. Unified Protocol and Affect Phobia Therapy have to our knowledge never been compared with each other, which this study aims to accomplish.The current study is a randomized controlled trial with a full factorial design. A total of 2400 participants will be divided into 12 different subgroups (2 * treatment duration [8 vs 16 weeks], 2 * discussion forum access [yes vs. no], and 3 * treatment [Unified Protocol vs. Affect Phobia Therapy vs. Waitlist).Inclusion criteria for the study are the following: Ability to read and write Swedish, access to smartphone or computer, minimum age of 18 years, and total GAD-7 ≥ 5 points and/or PHQ-9 ≥ 10 points.Exclusion criteria for the study are the following: Concurrent psychological treatment, initiation of or change in medication for anxiety or depression within the previous month, or self-reported severe depression (PHQ-9 total score ≥ 20) or suicidality (PHQ-9, item 9 > 2). Participants who report severe depression or suicidality will be excluded and recommended to seek other treatment.GAD7 and PHQ9 are the main outcome measures. Secondary measures are: Personality Inventory for DSM Short Form, Reflective Functioning Questionnaire 8, Negative Effects Questionnaire, and Brunnsviken Brief Quality of Life Scale.The study is still recruiting, but preliminary results will be available at the time of the SWErii conference.
  •  
29.
  • Carlbring, Per, et al. (författare)
  • Transdiagnostic Internet interventions : A breakthrough in psychological disorders?
  • 2023
  • Ingår i: Abstracts from the 12th Swedish Congress on internet interventions (SWEsrii), Uppsala University, Sweden. ; , s. 4-4
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Traditional evidence-based treatments for psychological disorders are often specific to one diagnosis. Some criticize this approach for not accounting for individual variation in symptoms. Transdiagnostic treatments aim to address this issue by being applicable to a wider range of patients. This study, called TRAbee, compares two transdiagnostic modalities: Unified Protocol (=Cognitive Behavior Therapy) and Affect Phobia Therapy (= Psychodynamic Psychotherapy). The study design is a randomized controlled trial with n=2400 participants who are divided into 12 subgroups based on treatment modality (CBT vs. PDT vs. waitlist), duration (8 or 16 weeks of treatment), and discussion forum access (yes/no). Participants were randomly assigned and measured weekly during treatment and then at 6, 12 and 24 months. Inclusion criteria: 18 years or older, ability to read/write Swedish, access to smartphone/computer, GAD-7 score ≥5, and/or PHQ-9 score ≥10. Exclusion criteria: current psychological treatment, recent medication change, severe depression/suicidality. Outcome measures include GAD7, PHQ9, PID- 5, RFQ-8, NEQ, and quality of life. Follow-up data is still being collected, but preliminary results including 12 month follow-up will be available at the SWErii conference.
  •  
30.
  • Carlbring, Per, et al. (författare)
  • Transdiagnostic self-help treatments for anxiety and/or depression : A full-factorial RCT investigating psychotherapeutic modalities, discussion boards and treatment length
  • 2022
  • Ingår i: International Society for Research onInternet Interventions 11th Scientific Meeting. ; , s. 19-19
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • ContextTypically, internet-based treatment programs are effective for a wide range of specific psychiatric diagnoses. However, diagnosing, and matching treatments to an individuals' need, is a challenge and potentially resource intensive. In this study, a computer automatically made the decision on inclusion and exclusion.Methods: A total of 2400 participants presenting with anxiety and/or depression were randomized into 12 subgroups (n=200 each) based on treatment modality (Cognitive Behavior Therapy vs. Psychodynamic Therapy vs. Waitlist), duration (8 vs. 16 weeks) and moderated discussion forum (Yes vs. No). Weekly measurements using PHQ9 and GAD7 were the primary outcome measures.Intervention (if relevant): Unified Protocol is a transdiagnostic Cognitive Behavior Therapy method for symptoms of anxiety and depression. The Affect Phobia treatment program was based on Psychodynamic models and treatment principles. The participants were also randomly assigned to either having (50%) or not having (50%) access to a discussion forum that was moderated by a clinician. Finally, all participants of the two treatment groups and the waitlist-control group were also randomly assigned to either an 8- or 16-week intervention duration.Results: All 2400 participants have been recruited. However, all post-assessment data is not yet collected at the time of writing (but will be by the time of the conference). The results will show if transdiagnostic treatment is better than a waitlist, if there is a relative difference between Cognitive Behavior Therapy and Psychodynamic treatment, if there is a relative difference between a 8 or 16 week long treatment, and if a discussion group has any added value.Conclusions: Since weekly assessment of outcome has been collected the statistical power is strong, especially since the total number of participants is 2400.Implications: The outcome will give a clear answer to several dissemination questions including treatment length, the added value of discussion boards and type of treatment (CBT vs. PDT).
  •  
31.
  • Classen, Jean-Francois, et al. (författare)
  • Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis
  • 2009
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1137-1144
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc. METHODS: Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center. RESULTS: Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal. CONCLUSION: The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.
  •  
32.
  • de Jong, R. S., et al. (författare)
  • 4MOST : Project overview and information for the First Call for Proposals
  • 2019
  • Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
  •  
33.
  • Ferrari, Raffaele, et al. (författare)
  • Frontotemporal dementia and its subtypes: a genome-wide association study.
  • 2014
  • Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
  •  
34.
  • Fischer, Gerhard, 1978, et al. (författare)
  • Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.
  • 2009
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.
  •  
35.
  • Gao, YX, et al. (författare)
  • Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
  • 2020
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
  • Tidskriftsartikel (refereegranskat)abstract
    • We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
  •  
36.
  • Gattinger, Pia, et al. (författare)
  • Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes
  • 2022
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:1, s. 230-242
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of critical importance for the design of effective vaccines and the evaluation of the degree of protective immunity conferred by exposure to the virus. As novel variants emerge, understanding their likelihood of suppression by population antibody repertoires has become increasingly important.Methods: In this study, we analyzed the SARS-CoV-2 polyclonal antibody response in a large population of clinically well-characterized patients after mild and severe COVID-19 using a panel of microarrayed structurally folded and unfolded SARS-CoV-2 proteins, as well as sequential peptides, spanning the surface spike protein (S) and the receptor-binding domain (RBD) of the virus.Results: S- and RBD-specific antibody responses were dominated by immunoglobulin G (IgG), mainly IgG1, and directed against structurally folded S and RBD and three distinct peptide epitopes in S2. The virus neutralization activity of patients´ sera was highly correlated with IgG antibodies specific for conformational but not sequential RBD epitopes and their ability to prevent RBD binding to its human receptor angiotensin-converting enzyme 2 (ACE2). Twenty percent of patients selectively lacked RBD-specific IgG. Only immunization with folded, but not with unfolded RBD, induced antibodies against conformational epitopes with high virus-neutralizing activity. Conformational RBD epitopes required for protection do not seem to be altered in the currently emerging virus variants.Conclusion: These results are fundamental for estimating the protective activity of antibody responses after natural infection or vaccination and for the design of vaccines, which can induce high levels of SARS-CoV-2–neutralizing antibodies conferring sterilizing immunity.
  •  
37.
  •  
38.
  • Gilmore, G., et al. (författare)
  • The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. Aims. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results. Methods. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. Results. The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. Conclusions. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
  •  
39.
  • Grundvattendagarna 2013
  • 2013
  • Proceedings (redaktörskap) (refereegranskat)abstract
    • Den här rapporten innehåller en sammanställning av abstracts som ligger till underlag för de presentationer som presenterades på konferensen Grundvattendagarna i Lund den 16–17 oktober 2013. Konferensen anordnades av SGU i samarbete med Geologiska institutionen på Lunds uni-versitet och Länsstyrelsen Skåne. Ett av konferensens syften var att få till en bred uppslutning från olika organisationer, myndigheter, konsulter, universitet, etc., och att skapa goda förutsättningar för att överföra kunskap och knyta kontakter för framtida samarbeten. Totalt har inte mindre än 59 olika bidrag kommit in och omfattningen på innehållet är verkligen stort. Det har varit en ära att få anordna konferensen och vi är tacksamma för det stora intresse som ni visat.
  •  
40.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
41.
  • Kloss, Frank, et al. (författare)
  • The role of oxygen termination of nanocrystalline diamond on immobilisation of BMP-2 and subsequent bone formation
  • 2008
  • Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:16, s. 2433-2442
  • Tidskriftsartikel (refereegranskat)abstract
    • Medical implants are increasingly often inserted into bone of frail patients, who are advanced in years. Due to age, severe trauma or pathology-related bone changes, osseous healing at the implant site is frequently limited. We were able to demonstrate that coating of endosseous implants with nanocrystalline diamond (NCD) allows stable functionalization by means of physisorption with BMP-2. Strong physisorption was shown to be directly related to the unique properties of NCD, and BMP-2 in its active form interacted strongly when NCD was oxygen-terminated. The binding of the protein was monitored under physiological conditions by single molecule force spectroscopy, and the respective adsorption energies were further substantiated by force-field-calculations. Implant surfaces refined in such a manner yielded enhanced osseointegration in vivo, when inserted into sheep calvaria. Our results further suggest that this technical advancement can be readily applied in clinical therapies with regard to bone healing, since primary human mesenchymal stromal cells strongly activated the expression of osteogenic markers when being cultivated on NCD physisorbed with physiological amounts of BMP-2.
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42.
  •  
43.
  • Landray, Martin J., et al. (författare)
  • Improving public health by improving clinical trial guidelines and their application
  • 2017
  • Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 38:21, s. 1632-1637B
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.
  •  
44.
  • Lilliengren, Peter, 1972-, et al. (författare)
  • Efficacy of Experiential Dynamic Therapy for Psychiatric Conditions : a Meta-Analysis of Randomized Controlled Trials
  • 2016
  • Ingår i: Psychotherapy. - : American Psychological Association (APA). - 0033-3204 .- 1939-1536. ; 53:1, s. 90-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Experiential dynamic therapy (EDT) is a subgroup of short-term psychodynamic psychotherapy (STPP) that emphasizes patients’ in-session affective processing. To evaluate the efficacy of EDT for psychiatric conditions, we conducted a meta-analysis of randomized controlled trials. Twenty-eight studies published between 1978 and 2014 were included, encompassing 1,782 adult patients with mood, anxiety, personality, or mixed disorders. Across targeted outcome domains, medium-size between-groups effects (Cohen’s ds ranging from 0.39 to 0.65) favored EDT over inactive controls at posttreatment and in symptom measures at follow-up. We found no differences between EDT and active treatments (e.g., medication, cognitive–behavioral therapy, manualized supportive therapy) at posttreatment, but EDT outperformed supportive therapy at follow-up (d = 0.75). In terms of within-group effect sizes, EDT was associated with large improvements in general psychiatric symptoms (d = 1.11), depression (d = 1.33), and anxiety (d = 1.09) and with small to moderate gains in the areas of interpersonal problems (d = 0.55) and global functioning (d = 0.86). Small but significant effects suggested continued improvement between posttreatment and follow-up. Heterogeneity in pre–post effects was explored in subgroup analyses, which indicated that EDT might be most effective in depressive disorders and that individual EDT had larger effects compared with group treatment. In addition, EDT performed better in higher quality studies. We conclude that EDT is a promising treatment for psychiatric conditions in adults. Further high-quality studies evaluating contemporary versions of EDT in specific psychiatric conditions are warranted.
  •  
45.
  • Lindqvist, Karin, et al. (författare)
  • Affect-Focused Psychodynamic Internet-Based Therapy for Adolescent Depression : Randomized Controlled Trial
  • 2020
  • Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR Publications Inc.. - 1438-8871. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adolescent depression is one of the largest health issues in the world and there is a pressing need for effective and accessible treatments.Objective: This trial examines whether affect-focused internet-based psychodynamic therapy (IPDT) with therapist support is more effective than an internet-based supportive control condition on reducing depression in adolescents.Methods: The trial included 76 adolescents (61/76, 80% female; mean age 16.6 years), self-referred via an open access website and fulfilling criteria for major depressive disorder. Adolescents were randomized to 8 weeks of IPDT (38/76, 50%) or supportive control (38/76, 50%). The primary outcome was self-reported depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR). Secondary outcomes were anxiety severity, emotion regulation, self-compassion, and an additional depression measure. Assessments were made at baseline, postassessment, and at 6 months follow-up, in addition to weekly assessments of the primary outcome measure as well as emotion regulation during treatment.Results: IPDT was significantly more effective than the control condition in reducing depression (d=0.82, P=.01), the result of which was corroborated by the second depression measure (d=0.80, P<.001). IPDT was also significantly more effective in reducing anxiety (d=0.78, P<.001) and increasing emotion regulation (d=0.97, P<.001) and self-compassion (d=0.65, P=.003). Significantly more patients in the IPDT group compared to the control group met criteria for response (56% vs 21%, respectively) and remission (35% vs 8%, respectively). Results on depression and anxiety symptoms were stable at 6 months follow-up. On average, participants completed 5.8 (SD 2.4) of the 8 modules.Conclusions: IPDT may be an effective intervention to reduce adolescent depression. Further research is needed, including comparisons with other treatments.Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 16206254; http://www.isrctn.com/ISRCTN16206254
  •  
46.
  • Lindqvist, Karin, et al. (författare)
  • Predictors of outcome in internet - delivered psychodynamic treatment for social anxiety
  • 2024
  • Ingår i: SweSRII 2024. - : Linköping University Electronic Press. ; , s. 13-14
  • Konferensbidrag (refereegranskat)abstract
    • INTRODUCTION: Guided self-help based on psychodynamic principles (IPDT) has shown efficacy for adolescent depression and non-inferiority to ICBT. Two randomized controlled trials have shown promising results for IPDT in Social Anxiety Disorder (SAD). There is little known regarding predictors of outcome in IPDT. This presentation focuses on predictors of  outcome in IPDT for SAD. METHODS: In this randomized controlled trial (n = 181), participants were randomized to guided IPDT, unguided IPDT or waitlist. Participants were recruited nationwide in Sweden. Eligible participants were ≥ 18 years old, scoring ≥ 60 on the Liebowitz Social Anxiety Scale self-report (LSAS-SR) without meeting any exclusion criteria. The IPDT intervention comprised eight self-help modules based on affect-focused dynamic therapy, delivered over 8 weeks on a secure online platform. The primary outcome was SAD symptom severity measured weekly by the LSAS-SR. Baseline measures such as comorbid symptoms of depression, anxiety, self-compassion, emotion regulation and defensive functioning were all tested as potential predictors of outcome. RESULTS: Preliminary findings will be presented at the conference. DISCUSSION: This is the second predictor study on IPDT and the first on IPDT for SAD. Finding predictors of outcome could lead to improved outcomes in terms of matching patients to the most effective treatment given their baseline characteristics.
  •  
47.
  • Lindqvist, Karin, et al. (författare)
  • Therapeutic alliance is calming and curing - The interplay between alliance and emotion regulation as predictors of outcome in Internet-based treatments for adolescent depression
  • 2023
  • Ingår i: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 91:7, s. 426-437
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Therapeutic alliance is one of the most stable predictors of outcome in psychotherapy, regardless of theoretical orientation. The alliance–outcome relationship in internet-based treatments has been investigated with mixed results. There is preliminary evidence that emotion regulation can work as a mediator for the alliance–outcome relationship. The present study aimed to investigate whether alliance predicted outcome session by session in two internet-based treatments for adolescent depression, and whether this relationship was mediated by emotion regulation.Method: Two hundred and seventy-two participants aged 15–19 years and diagnosed with depression were randomized to 10 weeks of internet-based psychodynamic or cognitive behavioral treatment. Both therapists and patients rated the alliance weekly. Patients also rated depressive symptoms and emotion regulation weekly. Analyses were made using cross-lagged panel modeling.Results: Alliance, as rated by both therapist and patient, predicted depression scores the following week. Emotion regulation rated by the patient also predicted depression scores the following week. Furthermore, alliance scores predicted emotion regulation scores the following week, which in turn predicted depression scores the week after, supporting the hypothesis that alliance influences outcome partly through emotion regulation. There were no group differences in any of these relationships.Conclusion: Alliance seems to play an important role in internet-based treatments, partly through emotion regulation. Clinicians working with text-based treatments should pay attention to the working alliance.
  •  
48.
  • Loser, Dominik, et al. (författare)
  • Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling
  • 2021
  • Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 95:12, s. 3695-3716
  • Tidskriftsartikel (refereegranskat)abstract
    • Several neonicotinoids have recently been shown to activate the nicotinic acetylcholine receptor (nAChR) on human neurons. Moreover, imidacloprid (IMI) and other members of this pesticide family form a set of diverse metabolites within crops. Among these, desnitro-imidacloprid (DN-IMI) is of special toxicological interest, as there is evidence (i) for human dietary exposure to this metabolite, (ii) and that DN-IMI is a strong trigger of mammalian nicotinic responses. We set out here to quantify responses of human nAChRs to DN-IMI and an alternative metabolite, IMI-olefin. To evaluate toxicological hazards, these data were then compared to those of IMI and nicotine. Ca2+-imaging experiments on human neurons showed that DN-IMI exhibits an agonistic effect on nAChRs at sub-micromolar concentrations (equipotent with nicotine) while IMI-olefin activated the receptors less potently (in a similar range as IMI). Direct experimental data on the interaction with defined receptor subtypes were obtained by heterologous expression of various human nAChR subtypes in Xenopus laevis oocytes and measurement of the transmembrane currents evoked by exposure to putative ligands. DN-IMI acted on the physiologically important human nAChR subtypes alpha 7, alpha 3 beta 4, and alpha 4 beta 2 (high-sensitivity variant) with similar potency as nicotine. IMI and IMI-olefin were confirmed as nAChR agonists, although with 2-3 orders of magnitude lower potency. Molecular docking studies, using receptor models for the alpha 7 and alpha 4 beta 2 nAChR subtypes supported an activity of DN-IMI similar to that of nicotine. In summary, these data suggest that DN-IMI functionally affects human neurons similar to the well-established neurotoxicant nicotine by triggering alpha 7 and several non-alpha 7 nAChRs.
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49.
  • Loser, Dominik, et al. (författare)
  • Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons
  • 2021
  • Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 95, s. 2081-2107
  • Tidskriftsartikel (refereegranskat)abstract
    • Neonicotinoid pesticides, originally developed to target the insect nervous system, have been reported to interact with human receptors and to activate rodent neurons. Therefore, we evaluated in how far these compounds may trigger signaling in human neurons, and thus, affect the human adult or developing nervous system. We used SH-SY5Y neuroblastoma cells as established model of nicotinic acetylcholine receptor (nAChR) signaling. In parallel, we profiled dopaminergic neurons, generated from LUHMES neuronal precursor cells, as novel system to study nAChR activation in human post-mitotic neurons. Changes of the free intracellular Ca2+ concentration ([Ca2+](i)) were used as readout, and key findings were confirmed by patch clamp recordings. Nicotine triggered typical neuronal signaling responses that were blocked by antagonists, such as tubocurarine and mecamylamine. Pharmacological approaches suggested a functional expression of alpha 7 and non-alpha 7 nAChRs on LUHMES cells. In this novel test system, the neonicotinoids acetamiprid, imidacloprid, clothianidin and thiacloprid, but not thiamethoxam and dinotefuran, triggered [Ca2+](i) signaling at 10-100 mu M. Strong synergy of the active neonicotinoids (at low micromolar concentrations) with the alpha 7 nAChR-positive allosteric modulator PNU-120596 was observed in LUHMES and SH-SY5Y cells, and specific antagonists fully inhibited such signaling. To provide a third line of evidence for neonicotinoid signaling via nAChR, we studied cross-desensitization: pretreatment of LUHMES and SH-SY5Y cells with active neonicotinoids (at 1-10 mu M) blunted the signaling response of nicotine. The pesticides (at 3-30 mu M) also blunted the response to the non-alpha 7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern.
  •  
50.
  • Löf, David, et al. (författare)
  • Structural Characterization of Nonionic Mixed Micelles Formed by C(12)EO(6) Surfactant and P123 Triblock Copolymer.
  • 2009
  • Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 113:16, s. 5478-5486
  • Tidskriftsartikel (refereegranskat)abstract
    • A structural characterization of mixed micelles formed in aqueous solution by the PEO-PPO-PEO triblock copolymer P123 and the nonionic surfactant C(12)EO(6) was carried out using various techniques, including ultralow shear viscosimetry, depolarized dynamic light scattering (VH-DLS), depolarized static light scattering (VH-SLS), and small-angle X-ray scattering (SAXS). The sphere-to-rod transition of the mixed micelles was studied in a diluted regime (P123 concentrations ranging from 0.5 to 10 wt %) at C(12)EO(6)/P123 molar ratios of 2.2, 3.2, 6.0, and 11 as well as for the pure C(12)EO(6). The data from VH-SLS and viscosimetry displayed a sharp increase in the intensity and viscosity, respectively, at the sphere-to-rod transition, and the results from the two methods were in accordance. In both techniques, an increased transition temperature with increasing content of C(12)EO(6) (in the molar ratio regime from 2.2 to 11) was observed. SAXS was used as the main technique, and a thorough structural characterization was performed, where indirect Fourier transformation (IFT) and generalized indirect Fourier transformation (GIFT) were employed in the analysis procedure of the SAXS data. The p(r) functions obtained from the IFT (employed at low P123 concentrations, i.e., 1.0 and 2.0 wt %) and GIFT (employed above 2.0 wt %) analyses revealed increased inhomogeneities in the mixed micelles when the molar ratio was increased. This suggested that the C(12)EO(6) organized themselves at the interface between the PPO core and the PEO corona of the P123 micelles, with the C(12) alkyl chain stretching into the hydrophobic core and the EO(6) part residing in the hydrophilic corona. The structure factor parameters obtained with GIFT for a molar ratio of 2.2 at a P123 concentration of 5.0 wt % showed radius values smaller than what was estimated from the p(r) functions. This was explained by an interpenetration of the PEO chains from one mixed micelle into a neighboring one. VH-DLS was performed on the mixed micelles at a temperature 3 degrees C above the transition temperature and at a molar ratio of 2.2. From the analyzed data, the average length L of the rods was estimated to be 102 nm.
  •  
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