956 resultados para Fourier analysis in several variables
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The availability of BRAF inhibitors has given metastatic melanoma patients an effective new treatment choice and molecular testing to determine the presence or absence of a BRAF codon 600 mutation is pivotal in the clinical management of these patients. This molecular test must be performed accurately and appropriately to ensure that the patient receives the most suitable treatment in a timely manner. Laboratories have introduced such testing; however, some experience low sample throughput making it critical that an external quality assurance programme is available to help promote a high standard of testing, reporting and provide an educational aspect for BRAF molecular testing. Laboratories took part in three rounds of external quality assessment (EQA) during a 12-month period giving participants a measure of the accuracy of genotyping, clinical interpretation of the result and experience in testing a range of different samples. Formalin fixed paraffin embedded tissue sections from malignant melanoma patients were distributed to participants for BRAF molecular testing. The standard of testing was generally high but distribution of a mutation other than the most common, p.(Val600Glu), highlighted concerns with detection or reporting of the presence of rarer mutations. The main issues raised in the interpretation of the results were the importance of clear unambiguous interpretation of the result tailored to the patient and the understanding that the treatment is different from that given to other stratified medicine programmes. The variability in reporting and wide range of methodologies used indicate a continuing need for EQA in this field.
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BACKGROUND: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. PATIENTS AND METHODS: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. RESULTS: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. CONCLUSIONS: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.
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Recent evidence suggests that - in addition to 17p deletion - TP53 mutation is an independent prognostic factor in chronic lymphocytic leukemia (CLL). Data from retrospective analyses and prospective clinical trials show that ∼5% of untreated CLL patients with treatment indication have a TP53 mutation in the absence of 17p deletion. These patients have a poor response and reduced progression-free survival and overall survival with standard treatment approaches. These data suggest that TP53 mutation testing warrants integration into current diagnostic work up of patients with CLL. There are a number of assays to detect TP53 mutations, which have respective advantages and shortcomings. Direct Sanger sequencing of exons 4-9 can be recommended as a suitable test to identify TP53 mutations for centers with limited experience with alternative screening methods. Recommendations are provided on standard operating procedures, quality control, reporting and interpretation. Patients with treatment indications should be investigated for TP53 mutations in addition to the work-up recommended by the International workshop on CLL guidelines. Patients with TP53 mutation may be considered for allogeneic stem cell transplantation in first remission. Alemtuzumab-based regimens can yield a substantial proportion of complete responses, although of short duration. Ideally, patients should be treated within clinical trials exploring new therapeutic agents.
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AIMS: Diagnosis of soft tissue sarcomas can be difficult. It can be aided by detection of specific genetic aberrations in many cases. This study assessed the utility of a molecular genetics/cytogenetics service as part of the routine diagnostic service at the Royal Marsden Hospital. METHODS: A retrospective audit was performed over a 15-month period to evaluate the diagnostic usefulness for soft tissue sarcomas with translocations of fluorescence in situ hybridisation (FISH) and reverse-transcriptase PCR (RT-PCR) in paraffin-embedded (PE) material. Results were compared with histology, and evaluated. RESULTS: Molecular investigations were performed on PE material in 158 samples (total 194 RT-PCR and 174 FISH tests), of which 85 were referral cases. Synovial sarcoma, Ewing sarcoma and low-grade fibromyxoid sarcoma were the most commonly tested tumours. Myxoid liposarcoma showed the best histological and molecular concordance, and alveolar rhabdomyosarcoma showed the best agreement between methods. FISH had a higher sensitivity for detecting tumours (73%, compared with 59% for RT-PCR) with a better success rate than RT-PCR, although the latter was specific in identifying the partner gene for each fusion. In particular, referral blocks in which methods of tissue fixation and processing were not certain resulted in higher RT-PCR failure rates. CONCLUSIONS: FISH and RT-PCR on PE tissue are practical and effective ancillary tools in the diagnosis of soft tissue sarcomas. They are useful in confirming doubtful histological diagnoses and excluding malignant diagnoses. PCR is less sensitive than FISH, and the use of both techniques is optimal for maximising the detection rate of translocation-positive sarcomas.
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In this study, we used IGH sequence analysis to assess the maturational status of Waldenstrom's (WM) macroglobulinemia and its putative precursor immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS). IGH sequence analysis was performed using standard methods in 23 cases (20 WM and 3 IgM MGUS as defined by consensus panel criteria). Waldenstrom's macroglobulinemia cases were characterized by heavily mutated IGH genes (median, 6.3%; range, 3.8%-13.9%) but without intraclonal variation (ICV). IgM MGUS was similarly characterized by somatic hypermutation (median, 7.5%; range, 7%-7.7%), but ICV was evident in 1 of the 3 cases. We would therefore conclude that WM is characterized by somatic hypermutation without ICV, which supports a derivation from postgerminal center/memory B cells. IgM MGUS is also characterized by somatic hypermutation but, in a manner similar to IgA/IgG MGUS, can be associated with ICV, although the significance of this remains unclear.
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This paper discusses areas for future research opportunities by addressing accounting issues faced by management accountants practicing in hospitality organizations. Specifically, the article focuses on the use of the uniform system of accounts by operating properties, the usefulness of allocating support costs to operated departments, extending our understanding of operating costs and performance measurement systems and the certification of practicing accountants.
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Il seguente lavoro di tesi è nato durante un’attività di stage della durata di 7 mesi svolto all’interno della divisione Tea&Coffe di IMA S.p.A., azienda leader mondiale nella produzione di macchine automatiche per il confezionamento di prodotti farmaceutici, cosmetici, alimentari, tè e caffè. Le attività svolte si collocano all’interno di un progetto avviato da IMA per promuovere il passaggio ad un modello di industria necessariamente più evoluta, facendo leva sull’attitudine ad integrare e sviluppare nuove conoscenze e nuove tecnologie interdisciplinari e, allo stesso tempo, di massimizzare la sinergia tra le dimensioni tecnica ed economica, comportando una reale riduzione di sprechi nella filiera produttiva, commerciale ed ambientale. I moderni impianti di produzione devono infatti affrontare una sfida che li vede alla continua ricerca della produttività, ovvero di una produzione che remuneri velocemente e con ampi margini gli investimenti effettuati, della qualità dei prodotti e dei processi di produzione, ovvero della garanzia di soddisfacimento delle aspettative espresse ed inespresse del cliente, e della sicurezza per la salvaguardia della collettività e dell’ambiente. L’obiettivo di questo elaborato è stato quello di effettuare lo studio affidabilistico di una macchina automatica per la produzione di bustine di tè al fine di poterne studiare il suo comportamento al guasto e di elaborare in un secondo momento le politiche manutentive ottimizzate che ne permettano una gestione più efficiente. In questo ambito la macchina è stata scomposta in gruppi e sono stati esaminati tutti i pezzi di ricambio che sono stati richiesti in un arco temporale di durata pari a dieci anni, il fine è quello di poter individuare ed effettuare un’analisi affidabilistica dei componenti critici per poi procedere, attraverso l’uso di piattaforme software quali Weibull++ e Blocksim, col modellarne le distribuzioni statistiche e simulare il funzionamento del sistema nel suo complesso.
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In a world where students are increasing digitally tethered to powerful, ‘always on’ mobile devices, new models of engagement and approaches to teaching and learning are required from educators. Serious Games (SG) have proved to have instructional potential but there is still a lack of methodologies and tools not only for their design but also to support game analysis and assessment. This paper explores the use of SG to increase student engagement and retention. The development phase of the Circuit Warz game is presented to demonstrate how electronic engineering education can be radically reimagined to create immersive, highly engaging learning experiences that are problem-centered and pedagogically sound. The Learning Mechanics–Game Mechanics (LM-GM) framework for SG game analysis is introduced and its practical use in an educational game design scenario is shown as a case study.
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Thesis (Ph.D.)--University of Washington, 2016-08
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Thesis (Ph.D.)--University of Washington, 2016-08
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Effective school discipline practices are essential to keeping schools safe and creating an optimal learning environment. However, the overreliance of exclusionary discipline often removes students from the school setting and deprives them of the opportunity to learn. Previous research has suggested that students are being introduced to the juvenile justice system through the use of school-based juvenile court referrals. In 2011, approximately 1.2 million delinquency cases were referred to the juvenile courts in the United States. Preliminary evidence suggests that an increasing number of these referrals have originated in the schools. This study investigated school-based referrals to the juvenile courts as an element of the School-to-Prison Pipeline (StPP). The likelihood of school-based juvenile court referrals and rate of dismissal of these referrals was examined in several states using data from the National Juvenile Court Data Archives. In addition, the study examined race and special education status as predictors of school-based juvenile court referrals. Descriptive statistics, logistic regression and odds ratio, were used to analyze the data, make conclusions based on the findings and recommend appropriate school discipline practices.