Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Base

Procurement Risk Management in Beef Supply Chains

Procurement risk management in beef supply chain

Two-Wholesale-Price Contracts: Push, Pull, and Advance-Purchase Discount Contracts

The allocation of inventory ownership affects the inventory availability in a supply chain, which in turn determines the supply chain performance. In this paper, we consider a supplier-retailer supply chain in which the supplier starts production well in advance of the selling season, and the retailer is offered two ordering opportunities at different points in time. An early order is allowed before the supplier's production decision, and a late order is allowed after the completion of production and after observing the demand. When the two wholesale prices change, we illustrate how the inventory decision rights and ownership are shifted and/or shared between the two firms, resulting in push, pull, or advance-purchase discount contracts. We then characterize the complete set of Pareto-dominant contracts for any given two-wholesale-price contract. We find that Pareto improvement can be achieved when inventory ownership is shifted from individual to shared and sometimes vice versa. In the latter case, push contracts not only are more likely to offer Pareto improvement, but also can achieve higher supply chain efficiency than pull contracts. We also identify conditions that enable Pareto improvement by introducing a new ordering opportunity to firms that had been bound by a single ordering opportunity without renegotiating the existing wholesale price, and we demonstrate through a numerical study that the adoption of the new ordering opportunity can significantly improve supply chain efficiency. We show that such Pareto improvement is more likely to happen when demand is more volatile.Pareto improvement, contracting, pricing, advance purchase, newsvendor model

Flexible Payment Schemes in Hotel Business

Also presented at POMS-HK International Conference, 6-7 January 2011, Hong Kon

Who Benefits from Transshipment? Exogenous vs. Endogenous Wholesale Prices

This paper studies how transshipments affect manufacturers and retailers, considering both exogenous and endogenous wholesale prices. For a distribution system where a single manufacturer sells to multiple identical-cost retailers, we consider both the manufacturer being a price taker and the manufacturer being a price setter in a single-period setup under multivariate normal demand distribution. In the case of the manufacturer being a price taker, we provide several analytical results regarding the effects of key parameters on order quantities and profits. In the case of the manufacturer being a price setter, we characterize the Stackelberg game that arises, and provide several insights into how the game dynamics are affected by transshipments. Specifically, we find that risk pooling makes retailers' order quantities less sensitive to the wholesale price set by the manufacturer; hence, in general, the manufacturer benefits from retailers' transshipments by charging a higher wholesale price, while retailers are often worse off. The paper captures the effect of demand correlation and the effect of the number of retailers throughout, and it illustrates the findings by a numerical example. We also provide an interactive Web page for numerical experiments.transshipment, multivariate normal distribution, demand correlation, Stackelberg equilibrium