Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.     

Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

Lanepitant is a high-affinity, selective neurokinin-1 receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine-associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant. Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.     

Computing steady-state mean time to failure for non-coherent repairable systems

Mean time to failure (MTTF) is an important reliability measure. Previous research is mainly concerned with the MTTF computation of coherent systems. In this paper, we derive equations to calculate the steady-state MTTF for noncoherent systems. Based on the equations, we extend the BDD by adding an intersection edge in each BDD node to efficiently store additional information for MTTF computation of noncoherent systems. A recursive algorithm is developed for MTTF computation using the extended BDD. To accelerate building the extended BDD, a method is proposed to avoid calculating the intersection edge for some nodes by keeping node monotonicity during the BDD construction. We show the efficiency of our algorithm by applying it to some example fault trees, real-life applications, and large fault tree benchmarks.     

The development of solidification microstructures in the presence of lateral constraints

The effect of a sudden change in cross section on the microstructural development has been investigated by the directional solidification technique. Experiments have been carried out in a transparent model system of succinonitrile-acetone so that the dynamical changes in the interface shapes can be monitoredin situ as the interface travels from a region of uniform cross section to a region of sharply reduced cross section. Different experimental conditions which give rise to initial steady-state planar, cellular, and dendritic interfaces have been investigated. Significant changes in microstructures have been observed as the interface approaches a sharply reduced cross section. The planar interface undergoes transitions to cellular and dendritic morphologies as the cross section is reduced, and reverse transitions are observed as the cross section is then increased gradually to its original value. An initial cellular interface is found to become dendritic as the cross section is reduced, and again it becomes cellular as the cross section is increased. When the experimental conditions are designed to give initial dendritic structures, the change in microstructure is found to occur only when the reduced cross section is of the order of primary dendrite spacing. When the reduced cross section is more than about 5 times the primary spacing, no appreciable change is observed in the dendritic array which travels across the cross-sectional change. The dynamical changes in the interface shape and the microstructural transitions that occur with the change in cross section have been examined quantitatively and discussed. Formerly with Ames Laboratory