Background: Older adults with acute myeloid leukemia (AML) represent a cancer population in which disease-based risk factors, comorbidities, patient goals, and treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel, including patient representatives, that minimized bias from conflicts of interest. Clarity Research Group at McMaster University supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development and evaluation approach, including evidence-to-decision frameworks, to assess evidence and make recommendations. Results: The panel agreed on 9 critical clinical recommendations for managing AML in older adults, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management; traditional induction and postremission therapy vs hypomethylating agent or low-dose cytarabine, or combinations with venetoclax; the role and duration of postremission therapy; combinations with venetoclax vs monotherapy; the use of targeted therapy, including isocitrate dehydrogenase and FMS-like tyrosine kinase 3 (FLT3) inhibitors, in appropriate patients; the role of hematopoietic stem cell transplantation in nonfavorable prognosis AML; and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Key recommendations of these guidelines include treatment over best supportive care; venetoclax-based regimens over monotherapies; and incorporation of FLT3 inhibitors into traditional induction and postremission therapy.
NASA's Curiosity rover is exploring a 5 km tall sedimentary mound that is hypothesized to record the transition from a warm and wet (phyllosilicate-rich) to a cold and drier (sulfate-rich) Mars. Evidence of magnesium sulfate-bearing rock has shown that Curiosity has crossed through this phyllosilicate-sulfate transition. Recently, Curiosity arrived at the Amapari Marker Band, a darker, indurated unit that can be traced laterally for tens of kilometers in orbiter images. Here, Curiosity found evidence for a very broad lake, and bedforms interpreted as wave-ripple laminated sedimentary rock that likely was deposited in shallow water in the explored location, before becoming a deeper lake. These rocks are enriched in Fe, Mn, and Zn which has major implications for groundwater paleohydrology in Gale crater. Three formation hypotheses are considered: concretion formation during early diagenetic alteration of shallow lake sediments, laterization or leaching of the sediments, and addition of Fe, Mn, and Zn by a mildly acidic and reducing groundwater interacting with a redox and/or pH front in a stratified lake. The preferred interpretation of the metal enrichments within the Amapari Marker band sedimentary rocks is that they formed in a shallow water environment at a redox and/or pH front within the ripple unit, which drove precipitation and concentration of metals. If the enrichments are due to groundwater alteration, these processes could link subsurface and surface environments. Water and the presence of high amounts of redox sensitive elements and other metals are favorable indicators for habitability.
Aim The evolution of montane species provides critical insights into the drivers of adaptation and diversification. Topographic complexity, a defining feature of many mountainous landscapes, promotes ecological and geographic isolation, often accelerating speciation rates. However, the extent to which topographic complexity directly shapes diversification remains unresolved. Here, we investigate the evolutionary dynamics of Anolis lizards across Neotropical mountain ranges to test two hypotheses: (1) higher elevation environments promote higher speciation rates in species that inhabit them; and (2) greater topographic complexity and climatic stability (i.e., lower past climatic-change velocity) positively influence speciation rates.Location The Americas.Time Period Present.Major Taxa Studied Anolis lizards.Methods We gathered topographic complexity and past climatic-change velocity data for 303 anole species and performed phylogenetic analyses to assess how speciation rates change across mountain ranges in the Americas.Results We found that topographic complexity and past climatic-change velocity do not significantly influence speciation rates, diverging from prior studies that link rugged landscapes or past climatic-change velocity to high diversification rates.Main Conclusions Our findings challenge assumptions about the direct role of topographic complexity in speciation, highlighting the need to consider multifaceted ecological and biogeographical factors driving evolutionary processes. By disentangling the relative contributions of climatic stability (i.e., lower past climatic-change velocity) and topographic heterogeneity, this study highlights the complex dynamics shaping biodiversity in tropical mountains and calls for further integrative approaches to understand species diversification in the face of climatic and geological change.
Sodium-ion batteries (SIBs) provide a broader chemical design space for cathodes in terms of composition, crystal structure, and redox chemistry, yet current research largely remains confined to ordered layered frameworks. Recently, Li-excess cation-disordered rock-salt (DRX) cathodes have provided an alternative design space, enabled by their exceptional tunability in composition, stoichiometry, and stability/metastability. Inspired by these advances, we significantly expand the compositional space of Na-based cathodes by developing a series of metastable Na-based DRX cathodes based on Na-Ti-Mn-O systems spanning both stoichiometric and over-stoichiometric regimes. We reveal rich structural and chemical complexity arising from Na content and over-stoichiometry and demonstrate that unique local cation ordering motifs are closely correlated with enhanced anionic redox activity and Na-ion utilization. By systematically comparing the electrochemical and structural evolution of stoichiometric and over-stoichiometric compositions, we elucidate distinct metastability-driven mechanisms governing their electrochemical behavior. Our findings fill an important knowledge gap in metastable Na-based DRX chemistry.
CI chondrites are a compositionally primitive group of meteorites that have undergone extensive aqueous alteration, providing insights into the evolution of primitive planetesimals. Oued Chebeika 002 is the most pristine CI chondrite to date. In this work, we report its mineralogy, bulk chemistry, oxygen and potassium isotope ratios, and cosmogenic radionuclides 10Be, 26Al, and 36Cl. The 10Be cosmic ray exposure ages of Oued Chebeika 002 samples are 2.6 +/- 0.5 and 2.9 +/- 0.7 Myr. The delta 41K of two samples is -0.114 +/- 0.019 and -0.247 +/- 0.044 parts per thousand. We find that the mineralogy, oxygen isotopes, potassium isotopes, and bulk chemistry of Oued Chebeika 002 overlap with those of samples returned from the asteroids Ryugu and Bennu. We therefore propose that CI chondrites and the asteroids Bennu and Ryugu may have originated from a common parent body, for which we propose the name "Naunet," after an Egyptian goddess of primordial water. Naunet formed in the outer solar system and underwent aqueous alteration. In the main belt, Naunet broke up, producing rubble-pile asteroids, including Bennu, Ryugu, and the secondary CI chondrite parent body/bodies, fragments of which survived passage to the Earth's surface, becoming CI chondrites.
