International Contracts in European Courts: Jurisdiction Under Article 5(1) of the Brussels Convention

Background: Internet-based cognitive behavior therapy (ICBT) has shown promising effects in the treatment of irritable bowel syndrome (IBS). However, to date no study has used a design where participants have been sampled solely from a clinical population. We aimed to investigate the acceptability, effectiveness, and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic. less thanbrgreater than less thanbrgreater thanMethods: Sixty-one patients were randomized to 10 weeks of ICBT (n = 30) or a waiting list control (n = 31). The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training. Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale - IBS version (GSRS-IBS). Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion. Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling. less thanbrgreater than less thanbrgreater thanResults: Fifty of 61 patients (82%) completed the post-treatment assessment and 20 of 30 patients (67%) in the ICBT group were assessed at 12-month follow-up. The ICBT group demonstrated significantly (p andlt; .001) larger improvements on the IBS-related outcome scales than the waiting list group. The between group effect size on GSRS-IBS was Cohens d = 0.77 (95% CI: 0.19-1.34). Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors. Improvements in the ICBT group were maintained at 12-month follow-up. The ICBT condition was found to be more cost-effective than the waiting list, with an 87% chance of leading to reduced societal costs combined with clinical effectiveness. The cost-effectiveness was sustained over the 12-month period. less thanbrgreater than less thanbrgreater thanConclusions: ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic. However, many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred samples. ICBT may therefore be acceptable and effective for only a subset of clinical patients. Study dropout seemed to be associated with severe symptoms and large impairment. Objective and empirically validated criteria to select which patients to offer ICBT should be developed.Funding Agencies|Stockholm City Council||Stockholm Centre for Psychiatry Research, Linkoping University||Soderstrom-Konigska Foundation||Bror Gadelius Foundation|

Profits du commerce intercontinental et croissance dans la France du XVIIIe siècle

Cet article étudie le rôle du commerce intercontinental dans l’accumulation de capital en France à la fin de l’Ancien Régime. J’utilise la méthode de O’Brien pour mesurer la quantité annuelle de profits dégagée par ce secteur. En prenant en compte les utilisations alternatives des moyens de production du secteur utilisait, je calcule le gain net qui peut lui être attribué. Finalement, je propose une méthode originale pour mesurer son effet qui s’appuie sur la notion de « coeur de croissance ». Cet article montre que les profits du commerce intercontinental ont pu avoir une bien plus grande importance que ne le suggère leur valeur agrégée.This paper studies the role of French intercontinental trade in the accumulation of domestic capital at the end of the Ancien Régime. It uses O’Brien’s method to measure the amount of annual profits generated by this sector. The marginal gain linked to the existence of the sector is then computed by estimating what would have been the return of the resources the sector was using if they had been invested domestically instead. Finally, the paper uses the notion of “hearth of growth” to argue that profits from intercontinental trade were more important for the French economy than what their size suggests.This version is the pre-print of the published article

The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

<p>Abstract</p> <p>Background</p> <p>Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the <it>COMT </it>gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting.</p> <p>Methods</p> <p>We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients.</p> <p>Results</p> <p>We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material.</p> <p>Conclusions</p> <p>We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed.</p> <p>Trial registration</p> <p>Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, <url>http://www.clinicaltrials.gov/ct2/show/NCT00845260</url></p

Internet-Based Cognitive Behavior Therapy vs. Cognitive Behavioral Group Therapy for Social Anxiety Disorder: A Randomized Controlled Non-inferiority Trial

Background and Aims: Cognitive behavioral group therapy (CBGT) is an effective, well-established, but not widely available treatment for social anxiety disorder (SAD). Internet-based cognitive behavior therapy (ICBT) has the potential to increase availability and facilitate dissemination of therapeutic services for SAD. However, ICBT for SAD has not been directly compared with in-person treatments such as CBGT and few studies investigating ICBT have been conducted in clinical settings. Our aim was to investigate if ICBT is at least as effective as CBGT for SAD when treatments are delivered in a psychiatric setting. Methods: We conducted a randomized controlled non-inferiority trial with allocation to ICBT (n = 64) or CBGT (n = 62) with blinded assessment immediately following treatment and six months post-treatment. Participants were 126 individuals with SAD who received CBGT or ICBT for a duration of 15 weeks. The Liebowitz Social Anxiety Scale (LSAS) was the main outcome measure. The following non-inferiority margin was set: following treatment, the lower bound of the 95 % confidence interval (CI) of the mean difference between groups should be less than 10 LSAS-points. Results: Both groups made large improvements. At follow-up, 41 (64%) participants in the ICBT group were classified as responders (95% CI, 52%-76%). In the CBGT group, 28 participants (45%) responded to the treatment (95% CI, 33%-58%). At post-treatment and follow-up respectively, the 95 % CI of the LSAS mean difference was 0.68-17.66 (Cohens d between group = 0.41) and -22.51-15.69 (Cohens d between group = 0.36) favoring ICBT, which was well within the non-inferiority margin. Mixed effects models analyses showed no significant interaction effect for LSAS, indicating similar improvement across treatments (F = 1.58; df = 2, 219; p = .21). Conclusions: ICBT delivered in a psychiatric setting can be as effective as CBGT in the treatment of SAD and could be used to increase availability to CBT.Original Publication:Erik Hedman, Gerhard Andersson, Brjann Ljotsson, Erik Andersson, Christian Ruck, Ewa Mortberg and Nils Lindefors, Internet-Based Cognitive Behavior Therapy vs. Cognitive Behavioral Group Therapy for Social Anxiety Disorder: A Randomized Controlled Non-inferiority Trial, 2011, PLOS ONE, (6), 3, .http://dx.doi.org/10.1371/journal.pone.0018001Licensee: Public Library of Science (PLoS)http://www.plos.org

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Associations between cognition and serotonin receptor 1B binding in patients with major depressive disorder : a pilot study

The neurotransmitter serotonin has been widely implicated in the pathophysiology of major depressive disorder (MDD). In animal studies and human neuroimaging studies, involvement of the serotonin receptor 1B (5-HT1BR) in MDD and memory performance has been reported. However, the role of the 5-HT1BR in cognitive functions affected in MDD remains to be clarified. Ten patients with MDD diagnosis were examined with positron emission tomography (PET) and a battery of cognitive tests before and after Internet-based Cognitive Behavioral Therapy (ICBT). The results were compared to ten matched control subjects in order to investigate putative changes in 5-HT1BR availability and cognitive performance. Patients treated with ICBT showed statistically significant improvement relative to baseline in Verbal fluency, both letter and category production. Significant correlations were found between improvement in letter production and changes in 5-HT1BR availability in ventral striatum, between category production and amygdala, as well as between the improvement in Trailmaking test B and change in 5-HT1BR binding in dorsal brainstem, in amygdala and in hippocampus. The results suggest an association between 5-HT1BR binding and improvement in cognitive functioning. Replications in larger-scale studies are required to confirm these findings.Swedish Research Council (523-2013-2982)Birgitta and Sten WesterbergSwedish Society of MedicineStiftelsen Söderström-Königska sjukhemmetStockholm County CouncilThe Stockholm Centre for Psychiatric ResearchKarolinska InstitutetAccepte

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Amphetamine-evoked c- fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context

Dopamine (DA) and glutamate neurotransmission is thought to be critical for psychostimulant drugs to induce immediate early genes (IEGs) in the caudate-putamen (CPu). We report here, however, that the ability of DA and glutamate NMDA receptor antagonists to attenuate amphetamine-evoked c- fos mRNA expression in the CPu depends on environmental context. When given in the home cage, amphetamine induced c- fos mRNA expression predominately in preprodynorphin and preprotachykinin mRNA-containing neurons (Dyn-SP+ cells) in the CPu. In this condition, all of the D1R, D2R and NMDAR antagonists tested dose-dependently decreased c- fos expression in Dyn-SP+ cells. When given in a novel environment, amphetamine induced c- fos mRNA in both Dyn-SP+ and preproenkephalin mRNA-containing neurons (Enk+ cells). In this condition, D1R and non-selective NMDAR antagonists dose-dependently decreased c- fos expression in Dyn-SP+ cells, but neither D2R nor NR2B-selective NMDAR antagonists had no effect. Furthermore, amphetamine-evoked c- fos expression in Enk+ cells was most sensitive to DAR and NMDAR antagonism; the lowest dose of every antagonist tested significantly decreased c- fos expression only in these cells. Finally, novelty-stress also induced c- fos expression in both Dyn-SP+ and Enk+ cells, and this was relatively resistant to all but D1R antagonists. We suggest that the mechanism(s) by which amphetamine evokes c- fos expression in the CPu varies depending on the stimulus (amphetamine vs. stress), the striatal cell population engaged (Dyn-SP+ vs. Enk+ cells), and environmental context (home vs. novel cage).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66272/1/j.1471-4159.2003.01815.x.pd

Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial

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.Original Publication:Erik Andersson, Brjann Ljotsson, Filip Smit, Björn Paxling, Erik Hedman, Nils Lindefors, Gerhard Andersson and Christian Ruck, Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial, 2011, BMC PUBLIC HEALTH, (11), 215.http://dx.doi.org/10.1186/1471-2458-11-215Licensee: BioMed Centralhttp://www.biomedcentral.com