Protective factors as uni- or bipolar factors and their incremental validity and accuracy in predicting general recidivism

This study examined whether protective factors are unique or the opposite of risk factors and whether they have incremental validity in the prediction of general recidivism. Using a sample of 3306 Dutch forensic outpatients, this study was the first large-sample study ever performed on this topic. Results from exploratory factor analyses demonstrated a relatively stable factor structure of 14 factors, consisting of 32 of the initially included 68 risk factors and 11 of the initially included 17 protective items. The protective factors were found to be either bipolar (i.e., mirror images of risk factors) or responsivity characteristics (i.e., motivation for treatment, cognitive disability). Incremental validity for the recidivism prediction was found in one factor with internal protective items (e.g., empathy, financial management, life goals). This factor decreased the recidivism risk by 6%. However, weak predictive accuracy was found for this factor. Implications for clinical forensic practice are discussed with special focus on the risk-need-responsivity model

Multidimensional family therapy reduces self-reported criminality among adolescents with a cannabis use disorder

Background. Multidimensional family therapy (MDFT) is an established treatment program for youth displaying multi-problem behavior. We examined if MDFT decreased criminal offending among cannabis abusing adolescents, as compared with individual psychotherapy (IP). Methods. In a Western-European randomized controlled trial comparing MDFT with IP, a sample of 169 adolescents with a cannabis disorder completed self-reports on criminal offending. Half indicated they had committed one or more criminal offenses in the 90 days before the baseline assessment. Follow-up assessments were at 6 and 12 months after randomization. Results. The proportion of adolescents reporting non-delinquency increased during the study period, most so in the MDFT condition. In addition, MDFT lowered the number of violent offenses more than IP. This difference was not seen for property crimes. Conclusions. In cannabis abusing adolescents, MDFT is an effective treatment to prevent and reduce criminal offending. MDFT outperforms individual psychotherapy for violent crimes.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Granuloma formation in pulmonary sarcoidosis

Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells in Vitro, Ex Vivo and in Vivo

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies

Klimaatsnormen voor mestvarkens

De klimaatsnormen voor varkens zijn herzien. Belangrijke conclusies vande werkgroep: bij opleg is de benodigde minimumtemperatuur veel hogerdan men denkt

Multidimensional family therapy decreases the rate of externalising behavioural disorder symptoms in cannabis abusing adolescents: Outcomes of the INCANT trial

Background: US-based trials have shown that Multidimensional Family Therapy (MDFT) not only reduces substance abuse among adolescents, but also decreases mental and behavioural disorder symptoms, most notably externalising symptoms. In the INCANT trial, MDFT decreased the rate of cannabis dependence among Western European youth. We now focus on other INCANT outcomes, i.e., lessening of co-morbidity symptoms and improvement of family functioning.Methods: INCANT was a randomised controlled trial comparing MDFT with individual therapy (IP) at and across sites in Berlin, Brussels, Geneva, The Hague, and Paris. We recruited 450 boys and girls aged 13 up to 18 years with a cannabis use disorder, and their parent(s), and followed them for 12 months. Mental and behavioural characteristics (classified as 'externalising' or 'internalising') and family conflict and cohesion were assessed.Results: From intake through 12 months, MDFT and IP groups improved on all outcome measures. Models including treatment, site, and referral source showed that MDFT outperformed IP in reducing externalising symptoms.Adolescents were either self-referred to treatment (mostly on the initiative from people close to the teen) or referred under some measure of coercion by an external authority. These two groups reacted equally well to treatment.Conclusions: Both MDFT and IP reduced the rate of externalising and internalising symptoms and improved family functioning among adolescents with a cannabis use disorder. MDFT outperformed IP in decreasing the rate of externalising symptoms. Contrary to common beliefs among therapists in parts of Western Europe, the 'coerced' adolescents did at least as well in treatment as the self-referred adolescents.MDFT shows promise as a treatment for both substance use disorders and externalising symptoms

Fibrocytes are increased in lung and peripheral blood of patients with idiopathic pulmonary fibrosis

Background: Fibrocytes are implicated in Idiopathic Pulmonary Fibrosis (IPF) pathogenesis and increased proportions in the circulation are associated with poor prognosis. Upon tissue injury, fibrocytes migrate to the affected organ. In IPF patients, circulating fibrocytes are increased especially during exacerbations, however fibrocytes in the lungs have not been examined. Therefore, we sought to evaluate if fibrocytes can be detected in IPF lungs and we compare percentages and phenotypic characteristics of lung fibrocytes with circulating fibrocytes in IPF. Methods: First we optimized flow cytometric detection circulating fibrocytes using a unique combination of intra- and extra-cellular markers to establish a solid gating strategy. Next we analyzed lung fibrocytes in single cell suspensions of explanted IPF and control lungs and compared characteristics and numbers with circulating fibrocytes of IPF. Results: Using a gating strategy for both circulating and lung fibrocytes, which excludes potentially contaminating cell populations (e.g. neutrophils and different leukocyte subsets), we show that patients with IPF have increased proportions of fibrocytes, not only in the circulation, but also in explanted end-stage IPF lungs. These lung fibrocytes have increased surface expression of HLA-DR, increased intracellular collagen-1 expression, and also altered forward and side scatter characteristics compared with their circulating counterparts. Conclusions: These findings demonstrate that lung fibrocytes in IPF patients can be quantified and characterized by flow cytometry. Lung fibrocytes have different characteristics than circulating fibrocytes and represent an intermediate cell population between circulating fibrocytes and lung fibroblast. Therefore, more insight in their phenotype might lead to specific therapeutic targeting in fibrotic lung diseases

Enhanced Bruton's tyrosine kinase in B-cells and autoreactive IgA in patients with idiopathic pulmonary fibrosis

RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is thought to be triggered by repeated alveolar epithelial cell injury. Current evidence suggests that aberrant immune activation may contribute. However, the role of B-cell activation remains unclear. We determined the phenotype and activation status of B-cell subsets and evaluated the contribution of activated B-cells to the development of lung fibrosis both in humans and in mice. METHODS: B-cells in blood, mediastinal lymph node, and lung single-cell suspensions of IPF patients and healthy controls (HC) were characterized using 14-color flow cytometry. Mice were exposed to bleomycin to provoke pulmonary fibrosis. RESULTS: More IgA+ memory B-cells and plasmablasts were found in blood (n = 27) and lungs (n = 11) of IPF patients compared to HC (n = 21) and control lungs (n = 9). IPF patients had higher levels of autoreactive IgA in plasma, which correlated with an enhanced decline of forced vital capacity (p = 0.002, r = - 0.50). Bruton's tyrosine kinase expression was higher in circulating IPF B-cells compared to HC, indicating enhanced B-cell activation. Bleomycin-exposed mice had increased pulmonary IgA+ germinal center and plasma cell proportions compared to control mice. The degree of lung fibrosis correlated with pulmonary germinal center B-cell proportions (p = 0.010, r = 0.88). CONCLUSION: Our study demonstrates that IPF patients have more circulating activated B-cells and autoreactive IgA, which correlate with disease progression. These B-cell alterations were also observed in the widely used mouse model of experimental pulmonary fibrosis. Autoreactive IgA could be useful as a biomarker for disease progression in IPF