Native Speaker Perceptions of Accented Speech: The English Pronunciation of Macedonian EFL Learners

The paper reports on the results of a study that aimed to describe the vocalic and consonantal features of the English pronunciation of Macedonian EFL learners as perceived by native speakers of English and to find out whether native speakers who speak different standard variants of English perceive the same segments as non-native. A specially designed computer web application was employed to gather two types of data: a) quantitative (frequency of segment variables and global foreign accent ratings on a 5-point scale), and b) qualitative (open-ended questions). The result analysis points out to three most frequent markers of foreign accent in the English speech of Macedonian EFL learners: final obstruent devoicing, vowel shortening and substitution of English dental fricatives with Macedonian dental plosives. It also reflects additional phonetic aspects poorly explained in the available reference literature such as allophonic distributional differences between the two languages and intonational mismatch

Molecular basis of inherited colorectal carcinomas in the Macedonian population: An update

Hereditary factors are assumed to play a role in ~35.0-45.0% of all colorectal cancers (CRCs) with about 5.0-10.0% associated with high penetrant disease-causing mutations in genes correlated to hereditary polyposis (HP) or hereditary non polyposis syndromes (HNPCC). Although inherited germline mutations in mismatch repair (MMR) and the APC genes contribute significantly to CRC, genetic diagnosis cannot yet be obtained in more than 50.0% of familial cases. We present updated data of 107 probands from the Macedonian population with clinically diagnosed HP (n = 41) or HNPCC (n = 66) obtained by next generation sequencing (NGS) with three different gene panels covering the coding, flanking and promoter regions of 114 cancer predisposition genes. Using this approach, we were able to detect deleterious mutations in 65/107 (60.7%) patients, 50.4% of which were in known well-established CRC susceptibility genes and 10.2% in DNA repair genes (DRG). As expected, the highest frequencies of deleterious variants were detected in familial adenomatous polyposis (FAP) and in HNPCC patients with microsatellite instability (MSI) tumors (93.8 and 87.1%, respectively). Variants of unknown significance (VUS) were detected in 24/107 (22.4%) patients, mainly in HNPCC patients with microsatellite stable (MSS) tumors or patients with oligopolyposis. The majority of VUS were also found in DRG genes, indicating the potential role of a doble-strand brake DNA repair pathway deficiency in colorectal cancerogenesis. We could not detect any variant in 18/107 (16.8%) patients, which supports the genetic heterogeneity of hereditary CRC, particularly in HNPCC families with MSS tumors and in families with oligopolyposis

Influence of MSI and 18q LOH markers on capecitabine adjuvant monotherapy in colon cancer patients

Nadica Matevska-Geshkovska,1 Marija Staninova-Stojovska,1 Aleksandra Kapedanovska-Nestorovska,1 Natalija Petrushevska-Angelovska,2 Milco Panovski,3 Biljana Grozdanovska,2 Nenad Mitreski,2 Aleksandar Dimovski1 1Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia; 2University Clinic for Oncology and Radiotherapy, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia; 3University Clinic for Abdominal Surgery, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia Purpose: The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients.Patients and methods: A total of 126 patients enrolled in a capecitabine Phase IV clinical trial were analyzed for microsatellite instability (MSI), 18q loss of heterozygosity (LOH), thymidylate synthase (TYMS) 5′ variable number of tandem repeat (VNTR), and methylene tetrahydrofolate reductase (MTHFR) C677T variants. The significance in predicting 5-year DFS/OS was assessed by Kaplan–Meier and Cox regression analyses.Results: The MSI-high (MSI-H) genotype was significantly associated with DFS (HR 0.205, 95% CI 0.05–0.88, P=0.033) and OS (HR 0.208, 95% CI 0.05–0.89, P=0.035) compared to the microsatellite stable genotype. In models stratified according to clinicopathologic characteristics, the MSI-H genotype remained a positive predictive factor for DFS/OS only in patients with stage III (P=0.023) and patients with tumors localized proximally to the splenic flexure (P=0.004). Distal colon cancers with 18q LOH have a greater survival rate when treated with capecitabine than patients with stable tumors (81.3% vs 50.0%, HR for relapse 0.348, 95% CI 0.13–0.97, P=0.043). TYMS 5′VNTR and MTHFR C677T variants were not associated with DFS or OS.Conclusion: MSI and 18q LOH markers have the potential to be utilized in the selection of colon cancer patients eligible for capecitabine adjuvant monotherapy. Keywords: gastrointestinal cancer, microsatellite instability, 18q allelic imbalance, prognostic marker&nbsp

E-learning as a tool to harmonize education and good quality assurance system in radiopharmacy

Porpose Basic education in radiopharmacy in an essential component of the scientific and technical background of a radiopharmacist and the inescapable route by which quality assurance in radiopharmacy can be implemented. The purpose of this study was to evaluate e-learning as a method to improve worldwide education in radiopharmacy and increase the awarness about concepts pertaining the quality of radiopharmaceuticals. Design and Methodology to establish e-learning platform designed as an innovative learning apparatus that, working along side conventional teaching methods, integrates education in all aspects of Radiopharmacy into the curricula being offered by universities at existing education and training institutions is the step forward to the global recognition of the unified standards. In this study, a few lines of analysis for developing a suitable e-learning platform in radiopharmacy were as follows: -Course flexibility to improve access and personalization by Students, rigorous definition of basic concepts and methods according to international standards, significantly decrease costs for education in radiopharmacy, enable fast practical implementation of theoretical concepts through virtual laboratory, building up a worldwide available, virtual repoitory of learning resourced in radiopharmacy. findings. Each module is designed as a "basic unit of knowledge", comprising a group of minimum competencies and knowledge about a specific subject and used independently or in combination with other modules or training resources, students can select the module and the time that best suits his/her professional needs for accessing the material. diversity and interactions between different educational contexts are exploited to increase harmonization and integration