Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression: a prospective, open-label, multicenter, randomized, phase 3 study

Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size

Cable supported bridges : concept and design

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A polymorphism in NFKB1 is associated with improved effect of interferon-α maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

Interferon-alpha as maintenance therapy after high-dose therapy for multiple myeloma has been intensively debated during the last 30 years because several clinical studies have been published with conflicting results. In the present study, the authors addressed the question, of whether inborn variation in genes involved in inflammation influence treatment outcome in multiple myeloma patients receiving interferon-alpha as maintenance therapy. The findings suggest that a polymorphism in NFKB1 may be associated with improved effect of interferon-α in multiple myeloma patients, with homozygous carriers of the wild type allele having longer survival

The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP

International audienceThe gene was originally described as an inhibitor of RelA/p65 subunit of nuclear factor κB (NF-κB). Here, we analyse the association between genetic variation in the genes and and outcome of 348 myeloma patients treated with high-dose treatment (HDT), 146 patients treated with interferon-α (INF-α) as maintenance treatment, 177 patients treated with thalidomide, and 74 patients treated with bortezomib at relapse and address if the effects of polymorphisms in and are modified by a functional polymorphism in . By linkage disequilibrium mapping, we found that variant alleles of several polymorphisms in a sub-region of 19q13.3 spanning the regions -intron1-1 to intron1-3 and the region exon1 to exon3-6 in were associated with prolonged time-to-treatment failure (TTF;  = 0.003) and overall survival (OS;  = 0.02). Haplotype analyses revealed that none of the haplotypes were more strongly associated to TTF or OS than the two strongly linked SNPs, -intron1-1 (rs4572514) and (rs967591). The association of -intron1-1 and with TTF was independent of -94 ins/del, but homozygous ins-allele carriers which were also variant allele carriers of -intron1-1 or had the longest OS. Among patients treated with INF-α or thalidomide, no effect was seen in relation to genotype. Our results indicate that polymorphism in and are associated with outcome of myeloma patients treated with HDT. Combination analyses with the functional polymorphism in suggest that a possibly functional effect of or could be related to NF-κB availability

The Messina Strait Bridge: A Challenge and a Dream

This book describes the enormous depth of work carried out since the early seventies on the Messina Strait Bridge, up to the recent award of the detailed design and construction contract. This important work has included extensive studies, concepts and design developments, with far reaching applications, which have all confirmed the feasibility of this huge endeavour and have led to the optimisation of costs and expected performance levels. Attention is focused not only on the design itself, but also on the context for the project (e.g. historical, geological, seismo-tectonic and wind conditions; structural and mechanical properties; project management and financial aspects; and environmental considerations), and on the great challenges involved. Thus, considering the innovations and specific solutions adopted in overcoming the challenges presented by constructing a world record span of 3,300 metres at this site, it becomes clear how the Messina Strait Crossing will take its place as a masterpiece in bridge engineering history. This book will be of interest to bridge and structural engineers, geotechnical and wind engineers, mechanical and earthquake engineers, graduate students in all these areas and all others with a broad interest in bridge design and engineering