Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Systems to support health technology assessment (HTA) in member states of the European union with limited institutionalization of HTA

OBJECTIVES: The aim of this study was to support health technology assessment (HTA) capacity building in Member States of the European Union with limited experience or without institutionalized HTA. The main output is a Handbook on HTA Capacity Building. METHODS: The methods used were worldwide surveys of (i) HTA organizations, (ii) information management units, and (iii) HTA educational programs. The results of two surveys (i & ii) were combined with expert opinion to produce the Handbook on HTA Capacity Building. RESULTS: Survey of HTA organizations (n = 41, response rate 35 percent). Most of the organizations were established by the government (61 percent), and all were not-for-profit. Working on HTA (80.5 percent) and doing research (63.4 percent) were the main lines of activity. Survey on information management units (n = 23, response rate 23 percent). Most (74.2 percent) of the responding HTA agencies reported having personnel dedicated to HTA information services. Survey on HTA educational programs (n = 48, response rate 60 percent). In total, nine Master of Science (MSc) programs were identified (three MSc in HTA and six MSc in HTA-related areas). Handbook on HTA Capacity Building. A group of twenty experts from thirteen countries developed the handbook. It consists of nine chapters focusing on HTA institutional development (structural setup, work processes, and visibility). CONCLUSIONS: Setting up organizational structures and establishing effective HTA programs that guide key policy decisions is a challenging task. There are no standard models or pathways. 'One size fits all' is not a useful principle because of the wide systemic and cultural differences between countries. The Handbook on HTA Capacity Building includes approaches for overall institutional development, especially in formulating objectives, setting up structures, and defining work processe

Generation of HIV-1-specific T cells by electroporation of T-cell receptor RNA

BACKGROUND: HIV-1-specific cytotoxic T lymphocytes, which recognize conserved epitopes of the virus, are correlated with prolonged survival of infected individuals. Unfortunately, most HIV-1-infected patients are unable to generate such an immune response. Antigen-specific cytotoxic T lymphocytes can be generated by T-cell receptor transfer. This is commonly done by retroviral transduction, which is complicated and poses the threat of stable genetic alteration of autologous cells. METHODS: We reprogrammed primary CD8+ T cells by electroporation of RNA, which encoded an HIV-1-pol- and an HIV-1-gag-specific T-cell receptor recognizing the human leukocyte antigen-A2 restricted epitopes ILKEPVHGV and SLYNTVATL, respectively. RESULTS: These reprogrammed cells specifically produced the proinflammatory cytokines interleukin-2, tumor necrosis factor-alpha, and interferon-gamma after stimulation with target cells that presented the corresponding peptides, and were able to lyse these targets efficiently and specifically. The lytic avidities of the HIV-1-pol- and HIV-1-gag-TCR-RNA-electroporated CD8+ T cells were within the same range than those of the parental cytotoxic T lymphocytes. Most importantly, HIV-1-gag-reprogrammed T cells recognized target cells that presented endogenously processed antigen, which resulted in cytokine production and lysis. CONCLUSION: It is shown here for the first time that functional transfer of virus-specific T-cell receptors by RNA electroporation is feasible, and represents an innovative, safe, and easy method to generate virus-specific T cells, avoiding the risks of retroviral transduction

The portal vein as a distinct immunological compartment: A comprehensive immune phenotyping study

Advanced liver diseases are associated with impaired intestinal barrier function, which results in bacterial influx via the portal vein to the liver, causing hepatic and systemic inflammation. Little is known about possible concomitant trafficking of immune cells from the intestines to the liver. We therefore performed a comprehensive immunophenotyping study of the portal venous versus peripheral blood compartment in patients with liver cirrhosis who received a transjugular intrahepatic portosystemic stent shunt (TIPS). Our analysis suggests that the portal vein constitutes a distinct immunological compartment resembling that of the intestines, at least in patients with advanced liver cirrhosis. In detail, significantly lower frequencies of naïve CD4+ T cells, monocytes, dendritic cells and Vδ2 T cells were observed in the portal vein, whereas frequencies of activated CD4+ and CD8+ T cells, as well as of mucosa-associated Vδ1 T cells were significantly higher in portal venous compared to peripheral blood. In conclusion, our data raises interesting questions, e.g. whether liver cirrhosis-associated chronic inflammation of the intestines and portal hypertension promote an influx of activated intestinal immune cells like γδ T cells into the liver