Ixazomib-lenalidomide-dexamethasone in routine clinical practice: Effectiveness in relapsed/refractory multiple myeloma

[Aim]: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed.[Results]: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events.[Conclusion]: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1.This work was supported by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Phylogenetic evidence for the invasion of a commercialized European Phasmarhabditis hermaphrodita lineage into North America and New Zealand

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available

Cost reduction opportunities in induction surface hardening processes for smaller diameter cylindrical loads

This article focuses on the possibilities of improving the efficiency of induction surface hardening (ISH) processes using a specialized spray-quench device. This quench is fabricated using 3D printing, and the load is cooled by a quenching spray tangentially fed to its surface. Furthermore, the paper presents the results of several specific experiments which show how the tangential spray-quench device can influence the quenching phase of the ISH process. It is shown that the influence of the surface temperature of the load can be realized not only by the amount and type of quenching medium but also in what way the quenching medium is fed to the surface of the load

Experimentální hodnocení odolnosti proti výbuchu heterogenních kompozitních mostních plošin na bázi betonu

Because of the current geopolitical situation, research on improving the resistance of the civil and transport infrastructure to blast or impact loads has gained considerable attention. This paper presents the results of full-scale blast experiments designed to characterize the resistance of concrete-based composite bridge decks subjected to close-in blast loading. Three composite decks with different degrees of heterogeneity were proposed and tested: a slab with basalt fiber meshes in multiple layers along the depth of the specimen, a slab with recycled textile sheets 100 mm in total thickness, and a typical hollow-core prestressed slab. The dependence of the extent of the blast damage on the material characteristics of the composite material was studied. A detailed study of the damage to the specimen caused by the close-in explosion found apparent delamination of all tested composite specimens. The heterogeneity of the layered composite material converts the blast damage due to internal rebounds into layer delamination.Vzhledem ke současné geopolitické situaci si výzkum zaměřený na zlepšení odolnosti civilní a dopravní infrastruktury vůči výbuchu nebo nárazu vyžádal značnou pozornost. Tento článek představuje výsledky experimentů výbuchového zatěžování mostních betonových panelů. Byly navrženy a testovány tři kompozitní panely s různými stupni heterogenity: panel s čedičovými sítěmi ve více vrstvách, panel recyklovanými textilními vrstvami o celkové tloušťce 100 mm a typický panel s předpjatým dutým jádrem. Studována byla závislost rozsahu poškození výbuchem v závislosti na typu panelu. Poškození vzorku způsobené blízkou explozí vykazovalo zjevnou delaminaci kompozitních vrstev. Heterogenita vrstveného kompozitního materiálu převádí poškození výbuchem v důsledku vnitřních odrazů na delaminaci vrstev