Treatment of acute lymphoblastic leukemia. 30 years' experience at St. Jude Children's Research Hospital

BACKGROUND: Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. METHODS: To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). RESULTS: The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. CONCLUSIONS: The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae.     

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.     

MULTI-WALL CARBON NANOTUBE-BASED DNA NANOSENSOR FOR DETERMINING MITOXANTRONE-DNA INTERACTION IN-VITRO

The present study involves the development of a carbon nanotube based DNA nanosensor to determine the toxicological behavior of mitoxantrone (MTX). Mitoxantrone intercalates with DNA and produces a MTX-DNA adduct, resulting in the blockade of protein synthesis and excessive production of free radicals in the myocardium which eventually leads to cardiac toxicity. So, our work employs a DNA nanosensor to investigate the interaction of MTX with DNA. Multi-wall carbon nanotubes (MWCNTs) were functionalized with carboxyl group and were used for immobilization of DNA to construct the DNA nanosensor. The DNA nanosensor was immersed in MTX solution to monitor MTX-DNA interaction with respect to time and alter the resistance of the nanosensor. It was observed that MTX-DNA interaction is fast initially and as time elapses, the change in interaction gets slow due to formation of MTX-DNA adduct. The limit of detection (LOD) and limit of quantification (LOQ) were found as 150 (ng/mL) and 456 (ng/mL), respectively, for DNA nanosensor. This study suggests that the potentiometric nanosensor allows real-time monitoring of the drug-DNA interaction changes by measuring the potential at DNA/sensor interface which can prove to be an important tool in drug discovery pipelines and molecular toxicology.     

Evaluation of hot corrosion resistance of HVOF coatings on a Ni-based superalloy in molten salt environment

High-velocity oxy-fuel (HVOF) has the advantage of being a continuous and most convenient process for applying coatings to industrial installations at site. In this study, Cr₃C₂–NiCr, NiCrBSi, Stellite-6 and Ni–20Cr coatings were deposited on a Ni-based superalloy (19.5Cr–3Fe–0.3Ti–0.1C–balance Ni) using an HVOF process. Hot corrosion studies were performed on bare as well as coated superalloy specimens after exposure to a molten salt environment at 900 °C under cyclic conditions. The thermogravimetric technique was used to establish the kinetics of corrosion. XRD, SEM/EDAX and EPMA techniques were used to analyse the corrosion products. The hot corrosion resistance of all the coatings were superior to bare superalloy. Among the coatings studied, the Ni–20Cr coated superalloy imparted maximum hot corrosion resistance, whereas the Stellite-6 coated indicated minimum resistance. The hot corrosion resistance of all coatings may be attributed to the formation of oxides and spinels of nickel, chromium or cobalt.     

Obtaining mode mixity for a bimaterial interface crack using the virtual crack closure technique

We review, unify and extend work pertaining to evaluating mode mixity of interfacial fracture utilizing the virtual crack closure technique (VCCT). From the VCCT, components of the strain energy release rate (SERR) are obtained using the forces and displacements near the crack tip corresponding to the opening and sliding contributions. Unfortunately, these components depend on the crack extension size, Δ, used in the VCCT. It follows that a mode mixity based upon these components also will depend on the crack extension size. However, the components of the strain energy release rate can be used for determining the complex stress intensity factors (SIFs) and the associated mode mixity. In this study, we show that several—seemingly different—suggested methods presented in the literature used to obtain mode mixity based on the stress intensity factors are indeed identical. We also present an alternative, simpler quadratic equation to this end. Moreover, a Δ-independent strain energy release based mode mixity can be defined by introducing a “normalizing length parameter.” We show that when the reference length (used for the SIF-based mode mixity) and the normalizing length (used for Δ-independent SERR-based mode mixity) are equal, the two mode mixities are only shifted by a phase angle, depending on the bimaterial parameter ε.     

Scalable and QoS-Aware Dynamic Slot Assignment and Piconet Partitioning to Enhance the Performance of Bluetooth Ad Hoc Networks

Bluetooth is a radio technology for Wireless Personal Area Networks in the 2.4 GHz ISM frequency band and allows short-range devices to be connected in the form of ad hoc networks. The Bluetooth medium access control protocol is based on a strict master/slave concept wherein any communication between slave devices has to go through the master. While this model is simple, the use of such a nonoptimal packet forwarding scheme incurs much longer delays between any two slave-devices as double the bandwidth is used by the master. In addition, if two or more devices want to communicate as a group, this can only be achieved by either multiple unicast transmissions or a piconet-wide broadcast from the master. To handle these issues efficiently, we propose a novel combination of Dynamic Slot Assignment (DSA) and piconet partitioning. With DSA, the piconet master dynamically assigns slots to slaves so as to allow them to communicate directly with each other without any intervention from the master. Our proposed communication architecture provides for enhanced Quality of Service (QoS), better admission control, and multidevice conversation, which make a multicast-like communication feasible within the piconet. To widen the scope of DSA, we propose a QoS-aware Enhanced DSA (EDSA) version where dynamic piconet partitioning and scatternet support are exploited by grouping devices into piconets as per their connection endpoints, enabling it to be employed over a scatternet. We have performed extensive simulations and observe that these schemes drastically enhance Bluetooth performance in terms of the delay and the throughput, while significantly reducing the network power consumption.     

Segmented object manufacturing

Rapid Prototyping (RP) is a technology based on a “divide-and-conquer” strategy that enables automatic physical realization of a design without any special tooling. However, existing RP processes suffer from staircase defects since they are all based on 2.5-axis kinematics. To minimize the error due to staircase defects parts are normally built from very thin layers typically with thickness values of 0.010 to 0.300 mm. Therefore, hundreds of layers are required to produce a typical object making RP a slow and costly process. To overcome these limitations, a new RP process called Segmented Object Manufacturing (SOM) is proposed in this paper. SOM makes use of three-axis kinematics in conjunction with a novel slicing method. Slicing in SOM is based on certain visibility-based considerations and is independent of the part accuracy. Since only a few thick layers are used in the SOM technique, a part can be produced faster and cheaper with an accuracy comparable to that of CNC machining.     

Dynamic Modeling and Simulation of Impact in Tether Net/Gripper systems

The objective of this paper is to study the dynamic modeling andsimulation of a tether-net/gripper system during an impact, while it isbeing deployed or retrieved by a winch on a satellite orbiting aroundearth. We stick to Tether-Net system but the analysis is applicable toTether-Gripper systems too. We assume that the net is deployed from thesatellite in orbit and the motion is restricted to the orbital plane.This net captures a second satellite and tows it. The motion of atether-net system can be broken down into the following phases: (i)Phase 1: Net is shot out from the satellite with the tether completelyslack, (ii) Phase 2: Net comes to a location where the tether is tautwhile the drum on the orbiter is locked, (iii) Phase 3: Drum is unlockedand the net moves with the tether, (iv) Phase 4: Net captures a body.The continua (tether) is modeled using mode functions and coordinates.The theory of impulse and momentum can be used to model Phases 1, 2, and4 of motion of the tether-net system. The dynamics of the motion of thesystem in phase 3 is characterized by differential and algebraicequations (DAEs). Matlab ODE solvers were used to solve these DAEs.     

Effect of EGR on the exhaust gas temperature and exhaust opacity in compression ignition engines

In diesel engines, NOx formation is a highly temperature-dependent phenomenon and takes place when the temperature in the combustion chamber exceeds 2000 K. Therefore, in order to reduce NOx emissions in the exhaust, it is necessary to keep peak combustion temperatures under control. One simple way of reducing the NOx emission of a diesel engine is by late injection of fuel into the combustion chamber. This technique is effective but increases fuel consumption by 10–15%, which necessitates the use of more effective NOx reduction techniques like exhaust gas recirculation (EGR). Re-circulating part of the exhaust gas helps in reducing NOx, but appreciable paniculate emissions are observed at high loads, hence there is a trade-off between NOx and smoke emission. To get maximum benefit from this trade-off, a paniculate trap may be used to reduce the amount of unburnt particulates in EGR, which in turn reduce the paniculate emission also. An experimental investigation was conducted to observe the effect of exhaust gas re-circulation on the exhaust gas temperatures and exhaust opacity. The experimental setup for the proposed experiments was developed on a two-cylinder, direct injection, air-cooled, compression ignition engine. A matrix of experiments was conducted for observing the effect of different quantities of EGR on exhaust gas temperatures and opacity