Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.
The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available firstline). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
The rates for up-conversion intersystem crossing (UISC) from the T state to the S state are calculated for a series of organic emitters with an emphasis on thermally activated delayed fluorescence (TADF) materials. Both the spin-orbit coupling and the energy difference between the S and T states (ΔE) are evaluated, at the density functional theory (DFT) and time-dependent DFT levels. The calculated UISC rates and ΔE values are found to be in good agreement with available experimental data. Our results underline that small ΔE values and sizable spin-orbit coupling matrix elements have to be simultaneously realized in order to facilitate UISC and ultimately TADF. Importantly, the spatial separation of the highest occupied and lowest unoccupied molecular orbitals of the emitter, a widely accepted strategy for the design of TADF molecules, does not necessarily lead to a sufficient reduction in ΔE; in fact, either a significant charge-transfer (CT) contribution to the T state or a minimal energy difference between the local-excitation and charge-transfer triplet states is required to achieve a small ΔE. Also, having S and T states of a different nature is found to strongly enhance spin-orbit coupling, which is consistent with the El-Sayed rule for ISC rates. Overall, our results indicate that having either similar energies for the local-excitation and charge-transfer triplet states or the right balance between a substantial CT contribution to T and somewhat different natures of the S and T states, paves the way toward UISC enhancement and thus TADF efficiency improvement.
E ffective contact tracing is critical to controlling the spread of coronavirus disease (COVID-19) (1). South Korea adopted a rigorous contact-tracing program comprising traditional shoe-leather epidemiology and new methods to track contacts by linking large databases (global positioning system, credit card transactions, and closed-circuit television). We describe a nationwide COVID-19 contact tracing program in South Korea to guide evidence-based policy to mitigate the pandemic (2). The Study South Korea's public health system comprises a national-level governance (Korea Centers for Disease Control and Prevention), 17 regional governments, and 254 local public health centers. The first case of COVID-19 was identified on January 20, 2020; by May 13, a total of 10,962 cases had been reported.
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