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Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.

In deze bijdrage staat de vraag centraal of er een verband bestaat tussen tekstniveau in algemene voorwaarden aan de ene kant en claimverwachting en conflictbereidheid bij de consument aan de andere kant. Vertaalt eenvoudiger tekstniveau zich inderdaad in ander ‘denken, beslissen en doen’ bij de lezer? Gaan consumenten bij eenvoudiger tekstniveau in algemene voorwaarden anders denken en beslissen? Zouden ze inderdaad een ‘beter gevoel’ over de financiële dienstverlener krijgen en deze daarom anders tegemoet treden in geval van conflict? Een experiment onder 1542 Nederlanders laat inderdaad zien dat de claimverwachting groter is bij eenvoudiger tekstniveau en dat een hogere claimverwachting ook geassocieerd is met een hogere conflictbereidheid. Eenvoudiger tekst doet dus zeker ‘iets’ met verwachtingen van de lezer, maar ook onrechtstreeks met de conflictbereidheid. Deze bijdrage bespreekt de uitkomsten van het experiment en plaatst deze in de context van de discussie over eenvoudig taalgebruik in de financiële dienstverlening.

T cell-mediated cytotoxicity against Mycobacterium tuberculosis (MTB)-infected macrophages may be a major mechanism of specific host defense, but little is known about such activities in the lung. Thus, the capacity of alveolar lymphocyte MTB-specific cell lines (AL) and alveolar macrophages (AM) from tuberculin skin test-positive healthy subjects to serve as CTL and target cells, respectively, in response to MTB (H37Ra) or purified protein derivative (PPD) was investigated. Mycobacterial Ag-pulsed AM were targets of blood CTL activity at E:T ratios of > or = 30:1 (51Cr release assay), but were significantly more resistant to cytotoxicity than autologous blood monocytes. PPD- plus IL-2-expanded AL and blood lymphocytes were cytotoxic for autologous mycobacterium-stimulated monocytes at E:T ratios of > or = 10:1. The CTL activity of lymphocytes expanded with PPD was predominantly class II MHC restricted, whereas the CTL activity of lymphocytes expanded with PPD plus IL-2 was both class I and class II MHC restricted. Both CD4+ and CD8+ T cells were enriched in BL and AL expanded with PPD and IL-2, and both subsets had mycobacterium-specific CTL activity. Such novel cytotoxic responses by CD4+ and CD8+ T cells may be a major mechanism of defense against MTB at the site of disease activity.

CD4+ and gamma delta T cells are activated readily by Mycobacterium tuberculosis. To examine their role in the human immune response to M. tuberculosis, CD4+ and gamma delta T cells from healthy tuberculin-positive donor were studied for patterns of Ag recognition, cytotoxicity, and cytokine production in response to M. tuberculosis-infected mononuclear phagocytes. Both T cell subsets responded to intact M. tuberculosis and its cytosolic Ags. However, CD4+ and gamma delta T cells differed in the range of cytosolic Ags recognized: reactivity to a wide m.w. range of Ags for CD4+ T cells, and a restricted pattern for gamma delta T cells, with dominance of Ags of 10 to 15 kDa. Both T cell subsets were equally cytotoxic for M. tuberculosis-infected monocytes. Furthermore, both CD4+ and gamma delta T cells produced large amounts of IFN-gamma: mean pg/ml of IFN-gamma in supernatants was 2458 +/- 213 for CD4+ and 2349 +/- 245 for gamma delta T cells. By filter-spot ELISA (ELISPOT), the frequency of IFN-gamma-secreting gamma delta T cells was one-half of that of CD4+ T cells in response to M. tuberculosis, suggesting that gamma delta T cells on a per cell basis were more efficient producers of IFN-gamma than CD4+ T cells. In contrast, CD4+ T cells produced more IL-2 than gamma delta T cells, which correlated with diminished T cell proliferation of gamma delta T cells compared with CD4+ T cells. These results indicate that CD4+ and gamma delta T cell subsets have similar effector functions (cytotoxicity, IFN-gamma production) in response to M. tuberculosis-infected macrophages, despite differences in the Ags recognized, IL-2 production, and efficiency of IFN-gamma production.

Any system of consumer credit regulation is based both on conceptions of the legitimate function of credit in society and on assumptions pertaining to how creditors and debtors think, decide and operate. For instance, information disclosure duties in consumer regulation are predominantly based on the assumption that consumers are able to read and understand mandatorily disclosed information and that they are thus empowered to make better (rational) choices after having received information on the benefits and dangers of particular transactions. However, the concept of the well-informed, average consumer who only needs full information to choose alludes to a mythical figure. This seems especially true in the area of financial services because there the legislative framework hardly ever takes into account outright irrational consumer behaviour. Furthermore, where consumers face difficulties in processing information on credit or interest cost and terms, the complexities of credit products may provoke commercially profitable but dubious and deceptive practices. The provisions of the Directive 2008/48/EC on Credit agreements for consumers and repealing Council Directive 87/102/EEC (hereafter: EU Consumer Credit Directive) predominantly follow the abovementioned information paradigm. It promotes consumer autonomy by aiming at enabling consumers to make informed decisions. To this end, it imposes information duties on the creditor and credit intermediaries by means disclosure of information to be included in advertising with figures relating to the cost of credit and disclosure of information to be included in the credit agreements. Moreover, by using a Standard European Consumer Credit Information (hereafter: SECCI) it also regulates the form in which specific information must be conveyed to consumers in the pre-contractual stage. Such standardization of information appears to aim at avoiding information overload and at maintaining or allowing the comparability of different offers. Against this background, we will look into both the opportunities and the limitations of information disclosure duties encapsulated in the EU Consumer Credit Directive. Moreover, focusing on less-than-rational and cognitively distorted thinking and deciding involved in consumer borrowing behaviour, we draw attention to the question whether and to what extent information disclosure duties can actually improve the quality of contractual choice and lead to responsible borrowing. As the Directive aims at full harmonization, it leaves little room for manoeuvring at member state level. This may be at odds with the need felt by domestic policymakers for a more interventionist approach.

De laatste jaren is tekstbegrip van consumenten in de belangstelling gekomen in de wereld van financiële dienstverlening. Onduidelijkheid van productvoorwaarden, folders en brieven zou bijdragen aan wantrouwen in deze sector. Omgekeerd wordt vaak gedacht dat het verbeteren van duidelijkheid van teksten in het belang van de klant is en resulteert in het herstel van vertrouwen. Onderzoek laat echter zien dat het allemaal niet zo eenvoudig is. Tekstbegrip is een moeilijk waar te nemen fenomeen dat opgebouwd lijkt te zijn uit een complexe keten van contextafhankelijke variabelen. Bovendien is het verband tussen tekstbegrip en klantbelang niet evident. In deze bijdrage proberen we de materie te ontrafelen en te ordenen. Een aantal vragen staat daarbij centraal: Wat maakt dat mensen productvoorwaarden, algemene voorwaarden en soortgelijke juridisch relevante teksten wel of niet lezen? Wat is duidelijkheid van tekst en hoe meet je die bij juridische teksten? Is er verband tussen de mate van duidelijkheid van de tekst en consumentengedrag? In deze bijdrage geven we een overzicht van de wetenschappelijke literatuur op dit gebied en evalueren we de uitkomsten daarvan.

In this article, the authors analyse the Dutch Collective Settlement of Mass Damage Act (WCAM 2005) in light of the European developments concerning collective redress. Both the strong and weak points of the WCAM 2005 are discussed.

The predominant immunoregulatory activity of alveolar macrophages (AM) on T lymphocytes is to suppress their responses to antigenic and mitogenic stimuli. The suppressive activity of human AM for T cell responses to phytohemagglutinin (PHA) was further characterized. At ratios of AM to T lymphocytes of 0.4:1 to 1.6:1, AM inhibited the blastogenic response (3H-thymidine uptake into DNA) to PHA by 26 to 87%, respectively. Blood monocytes precultured in vitro for 5 to 7 days inhibited responses to PHA similarly. Freshly isolated blood monocytes, peritoneal macrophages, and A-549 epithelial and CCD-18Lu fibroblast cell lines failed to inhibit T lymphocyte responses. AM were capable of suppressing PHA-induced blastogenesis of purified CD4 cells without the addition of other cells. Cell contact was required for suppression of CD4 cells, as demonstrated using dual chambers. T cells precultured with AM with or without PHA retained the ability to respond to PHA compared with control T cells not precultured with AM. Kinetic experiments showed that AM needed to be added at the initiation of a 3-day culture period for suppression to occur. Analysis of the T cell DNA cycle revealed that AM decreased the percentage of cells entering the synthesis phase of DNA production. Flow cytometry also was used to assess the effect of AM on early markers of T cell activation. AM inhibited the percentage of T cells expressing the interleukin-2 receptor 46 to 83% and the transferrin receptor 58 to 78% at 24 to 48 h after stimulation with PHA. There was no effect of AM on expression of HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)