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

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The purpose of this study was to evaluate whether single-voxel (1)H MRS could add useful information to conventional MRI in the preoperative characterisation of the type and grade of brain tumours. MRI and MRS examinations from a prospective cohort of 40 consecutive patients were analysed double blind by radiologists and spectroscopists before the histological diagnosis was known. The spectroscopists had only the MR spectra, whereas the radiologists had both the MR images and basic clinical details (age, sex and presenting symptoms). Then, the radiologists and spectroscopists exchanged their predictions and re-evaluated their initial opinions, taking into account the new evidence. Spectroscopists used four different systems of analysis for (1)H MRS data, and the efficacy of each of these methods was also evaluated. Information extracted from (1)H MRS significantly improved the radiologists' MRI-based characterisation of grade IV tumours (glioblastomas, metastases, medulloblastomas and lymphomas) in the cohort [area under the curve (AUC) in the MRI re-evaluation 0.93 versus AUC in the MRI evaluation 0.85], and also of the less malignant glial tumours (AUC in the MRI re-evaluation 0.93 versus AUC in the MRI evaluation 0.81). One of the MRS analysis systems used, the INTERPRET (International Network for Pattern Recognition of Tumours Using Magnetic Resonance) decision support system, outperformed the others, as well as being better than the MRI evaluation for the characterisation of grade III astrocytomas. Thus, preoperative MRS data improve the radiologists' performance in diagnosing grade IV tumours and, for those of grade II-III, MRS data help them to recognise the glial lineage. Even in cases in which their diagnoses were not improved, the provision of MRS data to the radiologists had no negative influence on their predictions.