Prognostic significance of del 17p, ZAP-70 and CD38 as independent indicators for B-CLL: Correlation to response to treatment and disease outcome

Prognostic markers as CD38 and ZAP-70 and specific chromosomal abnormalities as del 17p have now been developed to refine the risk of progressive disease in chronic lymphocytic leukemia (CLL). This study analyzed 40 recently diagnosed, untreated B-CLL patients for CD38 and ZAP-70 expression by flow cytometry and for del 17p by conventional cytogenetics (CCG) and by fluorescence in situ hybridization (FISH) technique to evaluate their effect on the clinical course of CLL and as risk factors for disease progression in addition to their impact on response to treatment and disease outcome. Twenty healthy age- and sex-matched subjects were included as a control. The results revealed that CD38 and ZAP-70 expression were detected in 42.5% and 47.5% of cases, respectively. They were associated with an unfavorable clinical course. Higher levels were significantly associated with increased risk of unfavorable response to treatment (P = 0.003), with poor clinical outcome (P = 0.0001). Del 17p was detected in 35% of cases by FISH technique and in 7.5% by CCG. The deletion was significantly associated with progressive clinical course; poor response to treatment (P = 0.007) but not with disease outcome (P = 0.103). Combined analysis of ZAP-70 and CD38 yielded concordantly negative results in 50% of patients and concordantly positive results in 40% of patients, while 10% were discordant. CD38+/ZAP-70+ patients were significantly associated with progressive disease (P < 0.05) and with del 17p than CD38-/ZAP-70- patients (P = 0.008). Time to disease progression (TDP) was 6 months among CD38+/ZAP-70+ patients as compared to 16 months in CD38-/ZAP-70- patients. In patients with discordant results, the TDP was 9 months. Over-representation of the three parameters (CD38, ZAP-70 and del 17p) was detected in 22.5% of cases, and pointed towards even shorter TDP (4.5 months), more aggressive disease; more resistance to chemotherapy and poor outcome thus providing a precise tool for identifying high-risk patients. In conclusion, the combined expression of CD38 and ZAP-70 together with del 17p in CLL is a precise diagnostic tool for identifying high-risk patients and convey rapid progression; they are accurate predictors of clinical outcome thus could be used to indicate when more novel chemotherapeutic approaches are needed and provided help in guiding individual patient treatment.Keywords: CLL; CD38; ZAP-70; Del 17p; Immunophenotyping; FISH; Survival stud

A review of the distribution of particulate trace elements in urban terrestrial environments and its application to considerations of risk

We review the evolution, state of the art and future lines of research on the sources, transport pathways, and sinks of particulate trace elements in urban terrestrial environments to include the atmosphere, soils, and street and indoor dusts. Such studies reveal reductions in the emissions of some elements of historical concern such as Pb, with interest consequently focusing on other toxic trace elements such as As, Cd, Hg, Zn, and Cu. While establishment of levels of these elements is important in assessing the potential impacts of human society on the urban environment, it is also necessary to apply this knowledge in conjunction with information on the toxicity of those trace elements and the degree of exposure of human receptors to an assessment of whether such contamination represents a real risk to the city’s inhabitants and therefore how this risk can be addressed

Multi-physics modelling approach in all terrain vehicle longitudinal dynamics

This paper presents a detailed 4×4 off-road vehicle modelling method, based on a multi-physics approach. A full drivetrain system including all aspects of rotational inertial dynamics, friction, damping and stiffness properties is integrated with a fourteen-degrees-of-freedom vehicle model including body dynamics, kinematics, suspension and wheel dynamics as well as the terramechanical phenomena between tyres and soft soils. The interaction between all these modules is implemented in the MATLAB/SIMULINK/SimDriveline environment. The concepts of modularity, flexibility, and user-friendliness were emphasized during model development. The model is developed in order to provide design engineers with the capability to investigate effects of component selection and to develop control systems and automatic optimization processes for off-road 4×4 vehicles. While the modelling approach can be used for a wide variety of operating conditions, the present work focuses on the analysis of the contribution of different aspects on the off-road traction of 4×4 vehicles

Optimisation of AWD off-road vehicle performance using visco-lock devices

A comprehensive computer model is devised for the simulation of AWD off-road vehicle dynamics. Particular attention has been paid to the modelling of various visco-lock devices, including the viscous couplings and visco-lock limited-slip differentials. These devices are represented by fully parameterised physical models which capture the torque transmission mechanism represented by various thermodynamic, hydrodynamic, structural and mechanical modules. The characteristics of these devices can easily be altered so that comparisons can be made between different types. In addition, the influence of a wide range operating conditions, vehicle design parameters and tyre characteristics can also be made over various deformable soils