The addition of daratumumab to lenalidomide and dexamethasone resulted in superior response rate and progression-free survival, as compared with lenalidomide and dexamethasone alone, at a cost of ...more frequent neutropenia and infusion reactions.
The incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years,
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but most patients still eventually have a relapse.
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Relapse can occur even after standard complete remission in the context of first-line therapy, and studies are therefore evaluating deeper responses in a category termed “minimal residual disease–negative” (i.e., results below the threshold for minimal residual disease) that is prognostic with regard to a rate of disease progression in a time-to-event analysis and overall survival.
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However, this category of minimal residual disease status has . . .
Recent genomic studies have identified chromosomal rearrangements defining new subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL), however many cases lack a known initiating genetic ...alteration. Using integrated genomic analysis of 1,988 childhood and adult cases, we describe a revised taxonomy of B-ALL incorporating 23 subtypes defined by chromosomal rearrangements, sequence mutations or heterogeneous genomic alterations, many of which show marked variation in prevalence according to age. Two subtypes have frequent alterations of the B lymphoid transcription-factor gene PAX5. One, PAX5alt (7.4%), has diverse PAX5 alterations (rearrangements, intragenic amplifications or mutations); a second subtype is defined by PAX5 p.Pro80Arg and biallelic PAX5 alterations. We show that p.Pro80Arg impairs B lymphoid development and promotes the development of B-ALL with biallelic Pax5 alteration in vivo. These results demonstrate the utility of transcriptome sequencing to classify B-ALL and reinforce the central role of PAX5 as a checkpoint in B lymphoid maturation and leukemogenesis.
Fire emissions are critical for carbon and nutrient cycles, climate, and air quality. Dynamic Global Vegetation Models (DGVMs) with interactive fire modeling provide important estimates for long-term ...and large-scale changes of fire emissions. Here we present the first multi-model estimates of global gridded historical fire emissions for 1700-2012, including carbon and 33 species of trace gases and aerosols. The dataset is based on simulations of nine DGVMs with different state-of-the-art global fire models that participated in the Fire Modeling Intercomparison Project (FireMIP), using the same and standardized protocols and forcing data, and the most up-to-date fire emission factor table from field and laboratory studies over various land cover types. We evaluate the simulations of present-day fire emissions by comparing them with satellite-based products. Evaluation results show that most DGVMs simulate present-day global fire emission totals within the range of satellite-based products, and can capture the high emissions over the tropical savannas, low emissions over the arid and sparsely vegetated regions, and the main features of seasonality. However, most of the models fail to simulate the interannual variability, partly due to a lack of modeling peat fires and tropical deforestation fires. Historically, all models show only a weak trend in global fire emissions before ~1850s, consistent with multi-source merged historical reconstructions. The long-term trends among DGVMs are quite different for the 20th century, with some models showing an increase and others a decrease in fire emissions, mainly as a result of the discrepancy in their simulated responses to human population density change and land-use and land-cover change (LULCC). Our study provides a basic dataset for developing regional and global multi-source merged historical reconstructions and merging methods, and analyzing historical changes of fire emissions and their uncertainties as well as their role in the Earth system. It also highlights the importance of accurately modeling the responses of fire emissions to LULCC and population density change in reducing uncertainties in historical reconstructions of fire emissions and providing more reliable future projections.
We present a phenomenological theory of randomly cross-linked polymer networks based on the separation of solid-like and liquid-like degrees of freedom and taking into account the frozen ...inhomogeneity of network structure. The complete solution of the statistical mechanics of this model is given, and the monomer density correlation functions are calculated for neutral gels in good and ϑ solvents. The theoretical scattering curves are compared to the results of small angle neutron scattering and light scattering experiments, and new experimental tests of our theory are proposed.
Abstract Purpose We sought to project the number of primary care physicians required to meet US health care utilization needs through 2025 after passage of the Affordable Care Act. Methods In this ...projection of workforce needs, we used the Medical Expenditure Panel Survey to calculate the use of office-based primary care in 2008. We used US Census Bureau projections to account for demographic changes and the American Medical Association's Masterfile to calculate the number of primary care physicians and determine the number of visits per physician. The main outcomes were the projected number of primary care visits through 2025 and the number of primary care physicians needed to conduct those visits. Results Driven by population growth and aging, the total number of office visits to primary care physicians is projected to increase from 462 million in 2008 to 565 million in 2025. After incorporating insurance expansion, the United States will require nearly 52,000 additional primary care physicians by 2025. Population growth will be the largest driver, accounting for 33,000 additional physicians, while 10,000 additional physicians will be needed to accommodate population aging. Insurance expansion will require more than 8,000 additional physicians, a 3% increase in the current workforce. Conclusions Population growth will be the greatest driver of expected increases in primary care utilization. Aging and insurance expansion will also contribute to utilization, but to a smaller extent.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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