Purpose: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O 6 -Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance.The prognostic value of MGMTremains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Experimental Design: Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Results: Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio,1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMTexpression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Conclusions: Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMTexpression is a positive predictive marker in patients with anaplastic glioma.Anaplastic gliomas (WHO grade 3) show a wide variability of clinical outcome. Despite optimal treatment, mainly consisting of gross total resection followed by radiotherapy and chemotherapy with alkylating agents (1), therapeutic response and survival times vary considerably. This fact suggests that a large number of factors, including patient, tumor, and treatment characteristics, may influence the outcome (2 -4).Alkylating agents cause cell death by forming cross-links between adjacent strands of DNA due to alkylation of the O 6 position of guanine. The cellular DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) inhibits the cross-linking of double-stranded DNA by removing alkylating lesions (5 -7). A direct relationship between MGMT activity and resistance to alkylating nitrosoureas and methylating agents (i.e., ionizing radiations) has been well documented in cell lines and xenografts derived from a variety of human tumors, including gliomas (8). Moreover, depletion of MGMT activity with the substrate analogue inhibitor O 6

In many chemical and allied manufacturing systems, product quality is controlled based on postprocess quality inspection on sampled final products. Statistical analysis of the identified quality problems is then utilized to improve process operation, and thus the quality of succeeding products. Although this type of reactive quality control (QC) is necessary, it is not only inefficient because it “waits for” the occurrence of product quality problems, but also ineffective due to usually a significant time lag from problem identification, through solution derivation, to action taking. Furthermore, the derived solutions for problem solving are mostly heuristic in nature. This paper introduces a proactive product QC approach, which is established based on the concept of integrated product and process (IPP) control. Aiming at simultaneous dynamic control of process operation and product manufacturing, this approach ensures all‐time systematic control of both process performance and product quality. From the view point of both process control and product control, it is shown that IPP control can be realized by resorting to a well known scheme, cascade control. The IPP control problem for Single‐Input‐Single‐Output systems can be formulated rigorously, and the control laws can be identified readily. A synthesized IPP control system can effectively reject disturbances on the process and the product, and have excellent set‐point tracking capability, regardless of the type of interaction between the process and the product. The efficacy and attractiveness of the IPP control system design methodology are demonstrated through two types of case studies. © 2007 American Institute of Chemical Engineers AIChE J, 2007

The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.

We discuss the modeling of population kinetics of nonequilibrium steady-state plasmas using a collisional-radiative model and code based on analytical rates (ABAKO). ABAKO can be applied to low-to-high Z ions for a wide range of laboratory plasma conditions: coronal, local thermodynamic equilibrium or nonlocal thermodynamic equilibrium, and optically thin or thick plasmas. ABAKO combines a set of analytical approximations to atomic rates, which yield substantial savings in computer running time, still comparing well with more elaborate codes and experimental data. A simple approximation to calculate the electron capture cross section in terms of the collisional excitation cross section has been adapted to work in a detailed-configuration-accounting approach, thus allowing autoionizing states to be explicitly included in the kinetics in a fast and efficient way. Radiation transport effects in the atomic kinetics due to line trapping in the plasma are taken into account via geometry-dependent escape factors. Since the kinetics problem often involves very large sparse matrices, an iterative method is used to perform the matrix inversion. In order to illustrate the capabilities of the model, we present a number of results which show that the ABAKO compares well with customized models and simulations of ion population distribution. The utility of ABAKO for plasma spectroscopic applications is also outlined.