Upfront Treatment of FLT3-Mutated AML: A Look Back at the RATIFY Trial and Beyond.

In April 2017, following the results of the RATIFY trial (1), midostaurin, a multikinase FLT3 inhibitor, became the first FDA approved targeted agent for the treatment of acute myeloid leukemia (AML) (2). The addition of midostaurin to standard induction therapy with anthracycline and cytarabine (7 + 3) rapidly became the new standard of care for treatment-naïve, fit patients with FLT3-mutated (FLTmut+) AML (3). More recently, gilteritinib, a selective FLT3 inhibitor, showed superiority to chemotherapy in the treatment of relapsed or refractory FLTmut+ AML (4). With two FLT3 inhibitors now approved by the FDA—that is, the more selective gilteritinib and the less selective midostaurin—the question of which FLT3 inhibitor to use in combination with chemotherapy in the upfront setting has become the subject of much debate (5–7). Leukemia physicians are faced with the choice of using a more selective agent in the front line vs. reserving that agent for the time of relapse. Here, we evaluate the rationale for both approaches

Case-Analysis for Rippling and Inductive Proof

Rippling is a heuristic used to guide rewriting and is typically used for inductive theorem proving. We introduce a method to support case-analysis within rippling. Like earlier work, this allows goals containing if-statements to be proved automatically. The new contribution is that our method also supports case-analysis on datatypes. By locating the case-analysis as a step within rippling we also maintain the termination. The work has been implemented in IsaPlanner and used to extend the existing inductive proof method. We evaluate this extended prover on a large set of examples from Isabelle’s theory library and from the inductive theorem proving literature. We find that this leads to a significant improvement in the coverage of inductive theorem proving. The main limitations of the extended prover are identified, highlight the need for advances in the treatment of assumptions during rippling and when conjecturing lemmas

NOVEL GAS CLEANING/CONDITIONING FOR INTEGRATED GASIFICATION COMBINED CYCLE

Development efforts have been underway for decades to replace dry-gas cleaning technology with humid-gas cleaning technology that would maintain the water vapor content in the raw gas by conducting cleaning at sufficiently high temperature to avoid water vapor condensation and would thus significantly simplify the plant and improve its thermal efficiency. Siemens Power Generation, Inc. conducted a program with the Gas Technology Institute (GTI) to develop a Novel Gas Cleaning process that uses a new type of gas-sorbent contactor, the ''filter-reactor''. The Filter-Reactor Novel Gas Cleaning process described and evaluated here is in its early stages of development and this evaluation is classified as conceptual. The commercial evaluations have been coupled with integrated Process Development Unit testing performed at a GTI coal gasifier test facility to demonstrate, at sub-scale the process performance capabilities. The commercial evaluations and Process Development Unit test results are presented in Volumes 1 and 2 of this report, respectively. Two gas cleaning applications with significantly differing gas cleaning requirements were considered in the evaluation: IGCC power generation, and Methanol Synthesis with electric power co-production. For the IGCC power generation application, two sets of gas cleaning requirements were applied, one representing the most stringent ''current'' gas cleaning requirements, and a second set representing possible, very stringent ''future'' gas cleaning requirements. Current gas cleaning requirements were used for Methanol Synthesis in the evaluation because these cleaning requirements represent the most stringent of cleaning requirements and the most challenging for the Filter-Reactor Novel Gas Cleaning process. The scope of the evaluation for each application was: (1) Select the configuration for the Filter-Reactor Novel Gas Cleaning Process, the arrangement of the individual gas cleaning stages, and the probable operating conditions of the gas cleaning stages to conceptually satisfy the gas cleaning requirements; (2) Estimate process material & energy balances for the major plant sections and for each gas cleaning stage; (3) Conceptually size and specify the major gas cleaning process equipment; (4) Determine the resulting overall performance of the application; and (5) Estimate the investment cost and operating cost for each application. Analogous evaluation steps were applied for each application using conventional gas cleaning technology, and comparison was made to extract the potential benefits, issues, and development needs of the Filter-Reactor Novel Gas Cleaning technology. The gas cleaning process and related gas conditioning steps were also required to meet specifications that address plant environmental emissions, the protection of the gas turbine and other Power Island components, and the protection of the methanol synthesis reactor. Detailed material & energy balances for the gas cleaning applications, coupled with preliminary thermodynamic modeling and laboratory testing of candidate sorbents, identified the probable sorbent types that should be used, their needed operating conditions in each stage, and their required levels of performance. The study showed that Filter-Reactor Novel Gas Cleaning technology can be configured to address and conceptually meet all of the gas cleaning requirements for IGCC, and that it can potentially overcome several of the conventional IGCC power plant availability issues, resulting in improved power plant thermal efficiency and cost. For IGCC application, Filter-Reactor Novel Gas Cleaning yields 6% greater generating capacity and 2.3 percentage-points greater efficiency under the Current Standards case, and more than 9% generating capacity increase and 3.6 percentage-points higher efficiency in the Future Standards case. While the conceptual equipment costs are estimated to be only slightly lower for the Filter-Reactor Novel Gas Cleaning processes than for the conventional processes, the improved power plant capacity results in the potential for significant reductions in the plant cost-of-electricity, about 4.5% for the Current Standards case, and more than 7% for the Future Standards case. For Methanol Synthesis, the Novel Gas Cleaning process scheme again shows the potential for significant advantages over the conventional gas cleaning schemes. The plant generating capacity is increased more than 7% and there is a 2.3%-point gain in plant thermal efficiency. The Total Capital Requirement is reduced by about 13% and the cost-of-electricity is reduced by almost 9%. For both IGCC Methanol Synthesis cases, there are opportunities to combine some of the filter-reactor polishing stages to simplify the process further to reduce its cost. This evaluation has devised plausible humid-gas cleaning schemes for the Filter-Reactor Novel Gas Cleaning process that might be applied in IGCC and Methanol Synthesis applications

Simple, policy friendly, ecological interaction models from uncertain data and expert opinion

In the marine environment, humans exploit natural ecosystems for food and economic benefit. Challenging policy goals have been set to protect resources, species, communities and habitats, yet ecologists often have sparse data on interactions occurring in the system to assess policy outcomes. This paper presents a technique, loosely based on Bayesian Belief Networks, to create simple models which 1) predict whether individual species within a community will decline or increase in population size, 2) encapsulate uncertainty in the predictions in an intuitive manner and 3) require limited knowledge of the ecosystem and functional parameters required to model it. We develop our model for a UK rocky shore community, to utilise existing knowledge of species interactions for model validation purposes. However, we also test the role of expert opinion, without full scientific knowledge of species interactions, by asking non-UK based marine scientists to derive parameters for the model (non-UK scientists are not familiar with the exact communities being described and will need to extrapolate from existing knowledge in a similar manner to model a poorly studied system). We find these differ little from the parameters derived by ourselves and make little difference to the final model predictions. We also test our model against simple experimental manipulations, and find that the most important changes in community structure as a result of manipulations correspond well to the model predictions with both our, and non-UK expert parameterisation. The simplicity of the model, nature of the outputs, and the user-friendly interface makes it potentially suitable for policy, conservation and management work on multispecies interactions in a wide range of marine ecosystems

Flickertail Follies - 1951, Delta Gamma

The vocal trio from Delta Gamma\u27s performance of School Daze at the 1951 Flickertail Follies. Performers behind the trio compose the students of the classroom. Members of the trio are Marchetta Blackman, Beverly Welo, and Aurla Bettcher. Established by the Journalism Fraternity, Sigma Delta Chi, as a campus talent and variety show, The Flickertail Follies entertained the city of Grand Forks from 1925-1962. The Follies were, however, suspended from 1931-1935 due to The Depression and from 1941-1945 for World War II. The Follies gained national attention in 1950 when it was featured in Life Magazine . The show was dropped in 1962 but was revitalized for one year in 1982.https://commons.und.edu/archive-photos/1440/thumbnail.jp

Analysis of contamination - a must for ultraclean technology

Contamination analysis has become more and more important in recent years. The demands for purity of liquid chemicals, gases, wafers, and processing are increasing from generation to generation. Instead of requesting the same decrease for all impurities as is frequently done, see Table 1, a more specific procedure is necessary. The transfer of impurities from materials (liquid chemicals, gases, and equipment) onto wafers has to be measured by surface analysis and correlated to the impurities in the materials. This transfer depends on the properties of the wafer surface which have to be optimized. The concentration of impurities at the wafer surface or in a surface layer has to be correlated with devices properties and yield. After further processing then it will be possible to develop specifications which avoid an increase in quality of chemicals, gases, wafers, etc. without differentation thus making ultraclean processing affordable. Of cause in this context, cleaning is of utmost imp ortance, because it can help to clean up impurities after transfer, esp. in cases where the equipment is the cause of a contamination. When investigating the influence of contamination on devices, a clear distribution between the different types of devices is necessary. MOS devices are more sensitive against surface or interface properties whereas bipolar devices are more sensitive against volume properties. All these investigations are only possible by using contamination analysis as a key tool