Are the immuno-stimulatory properties of Lenalidomide extinguished by co-administration of Dexamethasone?

Dexamethasone has been a mainstay of anti-myeloma therapy for 20 years. However, it is intensely immunosuppressive and may limit the efficacy of the immune system to control myeloma, and limit the exciting opportunities to use immune stimulating drug therapies such as Lenalidomide to maximize the fight against this disease

Assessing the reliability and validity of an outcomes star

Purpose: This paper aims to assess the reliability, validity and use of the Family Star Plus, one of several Outcomes Stars increasingly used as part of outcomes-based accountability approaches in the delivery of family support services. The Family Star Plus measures progress towards effective parenting but a lack of evidence exists on its psychometric properties and suitability for use as an outcomes tool. Design/methodology/approach: Based on data from 1,255 families receiving a pilot support service, Cronbach’s alpha was used to assess the internal reliability of the 10-item scale, while principal component analysis (PCA) examined the number of constructs in the tool. Using matched data from evaluation of 80 families, correlations between the Family Star Plus and psychometrically validated tools were used to assess concurrent validity. Findings from a process evaluation explore practical issues around use of the tool. Findings: Cronbach’s alpha indicated sufficient internal reliability of the Family Star Plus; however, the PCA raised questions concerning the internal validity the Star. Correlations between the Star and validated tools were not strong enough to support concurrent validity of the Star. Process evaluation findings highlight inconsistencies in Family Star Plus data capture, which may explain these differences. Practical implications: Further work is required before the Family Star Plus can be considered for use as an outcome measure. Originality/value: To the best of authors’ knowledge, this is the first peer-reviewed analysis of the psychometric qualities of the Family Star Plus

A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of α4β7 integrin and an effector memory phenotype

AbstractIn this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response. SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group. SIV-Gag-specific CD8 T cells in the PB expressed α4β7 integrin, the gut-homing receptor; a minor subset co-express αEβ7 integrin. SIV-Gag-specific CD8 T cells were also detected in the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the duodenum and ileum. These cells were characterized by high levels of β7 integrin expression and a predominance of the effector memory phenotype. Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut. Thus, the DNA prime-oral Listeria boost strategy induced a mucosal SIV-Gag-specific CD8 T cell response characterized by expression of the α4β7 integrin gut-homing receptor

Social Innovation and Social Work:A Case Study of the Early Intervention Support Service

In a national and international context where there is a concern about the effectiveness of social care services for children and families to address chronic, enduring social problems and where there are finite resources available, the concept of social innovation in social work policy and practice to address need in new ways is receiving increased attention. While an attractive term, social innovation in child and family services is not without its challenges in terms of conceptualisation, operationalisation, implementation and evidencing impact. This article reports on the development and evaluation of the Early Intervention Support Service (EISS), a newly designed family support service in Northern Ireland set up as part of a government supported innovation and transformation programme that aims to deliver a voluntary, targeted, flexible and time limited service to families experiencing emergent problems. Using the EISS as a case study, the challenges, benefits in terms of addressing policy imperatives and future direction of social innovation in social work practice are reflected upon

Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting

Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. Results: ACTIV therapy induced durable complete remission of a variety of Her2+ tumors, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL-2, but were independent of IFN-gamma. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. Conclusions: This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissuesThis work was supported by grants from the Cancer Council of Victoria, Australia (1066554), The Peter MacCallum Cancer Center Foundation, and the National Health and Medical Research Council (NHMRC) of Australia (1103352). C.Y. Slaney and P. Beavis were supported by Postdoctoral Fellowships from the National Breast Cancer Foundation of Australia. A.J. Davenport and S. Mardiana received Postgraduate Scholarships from the Fight Cancer Foundation and University of Melbourne respectively. R.W. Johnstone and M.J. Smyth were supported by Senior Principal Research Fellowships from the NHMRC. M.H. Kershaw and P.K. Darcy were supported by Senior Research Fellowships from the NHMRC. S. Ellis was supported by a New Investigator Grant from the NHMR