A Multicenter Retrospective Chart Review Study of Treatment and Disease Patterns and Clinical Outcomes of Patients with Chronic-Phase Chronic Myeloid Leukemia in Third-Line Treatment or with T315I Mutation.

This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006-2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3-10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis.

A modelling-chain linking climate science and decision-makers for future urban flood management in West Africa.

Intensification of the hydrological cycle resulting from climate change in West Africa poses significant risks for the region's rapidly urbanising cities, but limited research on flood risk has been undertaken at the urban domain scale. Furthermore, conventional climate models are unable to realistically represent the type of intense storms which dominate the West African monsoon. This paper presents a decision-first framing of climate research in co-production of a climate-hydrology-flooding modelling chain, linking scientists working on state-of-the-art regional climate science with decision-makers involved in city planning for future urban flood management in the city of Ouagadougou, Burkina Faso. The realistic convection-permitting model over Africa (CP4A) is applied at the urban scale for the first time and data suggest significant intensification of high-impact weather events and demonstrate the importance of considering the spatio-temporal scales in CP4A. Hydrological modelling and hydraulic modelling indicate increases in peak flows and flood extents in Ouagadougou in response to climate change which will be further exacerbated by future urbanisation. Advances in decision-makers' capability for using climate information within Ouagadougou were observed, and key recommendations applicable to other regional urban areas are made. This study provides proof of concept that a decision-first modelling-chain provides a methodology for co-producing climate information that can, to some extent, bridge the usability gap between what scientists think is useful and what decision-makers need. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-022-01943-x.

Separation of diisopropylnaphthalene isomers.

The separation of diisopropylnaphthalenes was reinvestigated. The application of GCxGC appears to be a clear and necessary improvement over the use of single column techniques, with a polar (CP-Wax-52) column as reference technique, and a non-polar (CP-Sil-8) column as an alternative. Both qualitative and quantitative separations of DIPN isomers showed to be superior on GCxGC. The composition of both a DIPN mixture resulting from a typical experiment with a zeolite catalyst and a commercial one could be quantitatively determined in this way.

Community structure and dynamics of small eukaryotes targeted by new oligonucleotide probes: new insight into the lacustrine microbial food web.

The seasonal dynamics of the small eukaryotic fraction (cell diameter, 0.2 to 5 microm) was investigated in a mesotrophic lake by tyramide signal amplification-fluorescence in situ hybridization targeting seven different phylogenetic groups: Chlorophyceae, Chrysophyceae, Cryptophyceae, Cercozoa, LKM11, Perkinsozoa (two clades), and Fungi. The abundance of small eukaryotes ranged from 1,692 to 10,782 cells ml(-1). The dominant groups were the Chrysophyceae and the Chlorophyceae, which represented 19.6% and 17.9% of small eukaryotes, respectively. The results also confirmed the quantitative importance of putative parasites, Fungi and Perkinsozoa, in the small heterotrophic eukaryotic assemblage. The relative abundances recorded for the Perkinsozoa group reached as much as 31.6% of total targeted eukaryotes during the summer. The dynamics of Perkinsozoa clade 1 coincided with abundance variations in Peridinium and Ceratium spp. (Dinoflagellates), while the dynamics of Perkinsozoa clade 2 was linked to the presence of Dinobryon spp. (Chrysophyceae). Fungi, represented by chytrids, reached maximal abundance in December (569 cells ml(-1)) and were mainly correlated with the dynamics of diatoms, especially Melosira varians. A further new finding of this study is the recurrent presence of Cercozoa (6.2%) and LKM11 (4.5%) cells. This quantitative approach based on newly designed probes offers a promising means of in-depth analysis of microbial food webs in lakes, especially by revealing the phylogenetic composition of the small heterotrophic flagellate assemblage, for which an important fraction of cells are generally unidentified by classical microscopy (on average, 96.8% of the small heterotrophic flagellates were identified by the specific probes we used in this study).