Optimal use of targeted agents for advanced gastrointestinal stromal tumours.
ABSTRACT Imatinib is the recommended 1st-line treatment for a KIT-positive unresectable and/or metastatic gastrointestinal stromal tumour (GIST). However, some patients experience intolerance to imatinib and most patients will eventually experience disease progression while on imatinib treatment. Sunitinib is approved for treatment of a GIST after disease progression on, or intolerance to, imatinib therapy. Progression may occur early or later on, in treatment and is determined by factors including initial GIST genotype and mutational status. GISTs with KIT exon 11 mutations appear to be sensitive to standard dose imatinib, and patients with GISTs exhibiting KIT exon 9 mutations whose disease has progressed on imatinib 400 mg/day have been shown to respond to imatinib 800 mg/day, albeit with a higher incidence of adverse events. Sunitinib has shown clinical benefit in all major GIST mutational subtypes, particularly in patients with wild-type or KIT exon 9 genotype and against GISTs with secondary KIT exon 13 or 14 mutations. The choice between higher-dose imatinib and sunitinib after progression on standard dose imatinib is unclear, and apart from the GIST primary resistance genotype and mutational status, individual patient factors such as tumour characteristics, drug pharmacokinetics, and other clinical factors may affect response to treatment. Individualisation of therapy may help to maximise clinical benefit of therapy in these patients.
Conference Paper: Algorithms and design: the CRAY APP shared-memory system[Show abstract] [Hide abstract]
ABSTRACT: Analysis of fundamental algorithms of computational science drove the design of the CRAY APP system. The important characteristics central to many applications are exploited through the use of shared-memory programming techniques using existing compiler technology. A cluster-capable 84-processor system, the CRAY APP, provides a flat shared memory, low memory latency, fast barrier synchronization, and hardware-assisted parallel support. A patented crossbar/bus architecture provides system economy. Deterministic system behavior allows the compilers to view the system as a single virtual processor. For even higher performance, multiple CRAY APPs can be clustered. Cluster configurations may also contain a globally accessible memory. High-bandwidth low-latency connections allow this configuration to be effective for applications that require more performance than one CRAY APPCompcon Spring '93, Digest of Papers.; 03/1993
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ABSTRACT: In this paper, we tackle a new approach to the measurement and compensation of memoryless nonlinearities. It consists of three steps: i) the measuring of the amplitude distribution; ii) the orthogonal polynomial memoryless nonlinear description; and iii) the distortion compensation through algebraic polynomial inversion. With this procedure, an expeditious and rigorous method for the characterization of a nonlinear device is also possible with the important advantage of allowing for the use of far from ideal stimulus generators whose distortion can be compensated a posterioriAFRICON, 2004. 7th AFRICON Conference in Africa; 10/2004
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ABSTRACT: Though gastrointestinal stromal tumours are common, a duodenal stromal tumour is a rare entity. We present such a rare case with duodenal obstruction which caused a dilemma in the management of this patient. Though a Whipple’s operation was planned, intraoperatively, due to the pedunculated nature and free intraluminal mobility, resection of the polyp was done and histopathology was consistent with the diagnosis of a duodenal stromal tumour, which was reconfirmed with special stains/immunohistochemistry. Surgeons and pathologists should keep this rare primary tumour of the duodenum in mind as a differential diagnosis when examining/treating duodenal lesions, as a major surgical intervention can be avoided, cutting down on the cost, hospital stay, morbidity and mortality to the patient. A literature review and a discussion on the pertinent clinical, radiological, pathological and surgical aspects of stromal tumours have been discussed.