RESORT TURISTIK DHE HOTELIERI

Kosova edhe pse jo e pasur me pjesë bregdetare, ajo shquhet për malet e saja dhe për mundësi shfrytëzimi të tyre si pjesë e turizmit si ai verorë poashtu edhe ai dimërorë. Meqenëse si pikë kyqe kryesore për zhvillim të tij cilësohen resortet, pasiqë trend i tyre ka qenë dhe do të ngelet pozicionimi i tyre në natyrë, atëherë këto male kemi vendosur që ti shfrytezojmë në mënyren më të duhur që të cilësohen si atraksione në rajon duke sjellë në jetë këto vendstrehime me kushte europiane, të cilat janë në mungesë tek vendi ynë. Së bashku me zhvillimin e kësaj tematike, qëllim tjetër kryesorë është edhe zhvillimi i potencialit që ka Prevalla, e cila dihet që ka ngelur nën hijen e Brezovicës nga shkaqet që sjellë mungesa e infrastruktures. Evulimi i kësaj teme do të sjellë benefite shumë të mëdha, jo vetëm në anën e rrafshit të Dukagjinit por në të gjithë vendin

Can smart beta ETF's generate risk adjusted returns in the American stock market?

Denne oppgaven undersøker om smart beta ETF-er kan tilføre et godt alternativ til tradisjonelle fondsinvesteringer. Formålet med oppgaven er å teste om smart beta ETF-er genererer risikojustert meravkastning utover markedsindeksen i det amerikanske aksjemarkedet. Det vil også testes mot en portefølje bestående av tradisjonelle ETF-er som følger samme referanseindeks. Teorifundamentet i oppgaven baserer seg på resultater av tidligere forskning der man har tatt for seg om ulike risikofaktorer kan predikere avkastning. For å svare på problemstillingen deles smart beta ETF-ene i fem strategier, henholdsvis; dividende, likevektet, vekst, momentum og verdi. Smart beta-strategier søker hovedsakelig å utnytte faktorer som historisk har gitt en positiv avkastning, hvilket er godt dokumentert i empirisk forskning. Ved å bryte linken mellom pris og vekt i porteføljen vil smart beta ETF-ene forsøke å utnytte påviste prisanomalier i markedet. Strategiene blir testet ved bruk av Carharts firefaktormodell for å undersøke om de kan generere signifikante alfaverdier. Resultatet viste at ingen av smart beta-strategiene oppnådde positiv alfa som var signifikant forskjellig fra null når det justeres for markeds-, størrelse-, verdi- og momentumrisiko. Videre ble strategiene testet ved hjelp av sharpe-, treynor - og informasjonsraten. Studiens viktigste funn er at verdistrategien har gitt signifikant positiv informasjonsrate gjennom hele perioden og i perioden etter krisen. Dermed kan hypotesen om at verdistrategien genererer risikojustert meravkastning utover markedet støttes. For de andre smart beta-strategiene finner vi ingen signifikante meravkastningsrater og vi kan dermed ikke konkludere med at de er forskjellige fra null. For å svare på om smart beta ETF-er generer positiv avkastning målt mot andre investeringsalternativer har vi gjennomført en en-faktormodell mot ETF-er som har samme selvvalgte referanseindeks. I dette tilfellet fant vi signifikante resultater for alfa og for alle informasjonsratene bortsett fra, for vekstporteføljen. Dette innebærer at, dersom man ser bort i fra de ekstra honorarene genererer smart beta ETF-er risikojustert meravkastning relativt til tradisjonelle ETF-er.This thesis investigates whether Smart Beta ETF´s are a profitable investment strategy in the American stock market compared to traditional methods. Its objective is to observe if Smart Beta ETF’s can generate risk adjusted returns relative to the market index and their self-declared benchmark. The theoretical fundament is based on former research on the different factors that can predict returns. It also establishes a historical context and presents different theories, findings and former data’s on the subject. To answer our hypothesis, we categorize the smart beta ETF´s into five different strategies which we use as a basis for the analysis throughout the study; dividend, equal weighted, growth, momentum and value. The main goal for these strategies are tilt the portfolio towards their intended factor and in that way generate risk adjusted returns. Carhart’s model of four factors is applied to test whether the strategies generate alpha. Its performance will be measured according to sharpe rate, treynor rate and information rate. The most essential result in this thesis is that the value strategy has a significant positive information rate throughout the testing period and during the period after the crisis. This confirms the hypothesis; Smart Beta ETF, using the value strategy, generates risk adjusted returns relative to the market index. We do not find supporting evidence for the other strategies compared to the market index. Compared to the portfolio consisting of regular ETF´s following the same benchmark, we find that four out of five strategies get significant positive information ratios. This result may indicate that smart beta ETF´s are a better option that regular ETF´s, when transaction costs are not accounted for.M-Ø

Alfa Internexin Expression in a Series of 137 Gliomas and its Correlation with Oligodentroglial Morphology IDH1, P53 SYN and EGFR Expression

Background: Distinguishing glial subtypes based on nuclear and cellular morphology alone is subjective,with significant interobserver variability, even among highly experienced neuropathologists. Genetic subtyping of a given histological phenotype and robust biomarkers has improved the diagnostic and prognostic assessment. Recently, IDH1 (more rarely IDH2) mutations have been found in nearly 40% of gliomas and strongly predict lower grade in histology and better outcomes. Aim: To evaluate if the expression of alpha-internexin (INA) can be used a reliable diagnostic, prognostic and cost-effective marker, a proneural gene-coding neurofilament interacting protein significantly correlated with oligodendroglial phenotype, 1p/19q codeletion as well as higher chemosensitivity and better prognosis to our study population. Material: We studied INA expression in 137gliomasand correlated it with pure oligodendroglial histology, IDH1, p53, EGFR and SYN expression by immunohistochemistry.Results: INA was expressed in 72.2% of grade II oligodendrogliomas (n = 22), 62.5% of grade III oligodendrogliomas (n = 16), 57.2% of grade II oligoastrocytomas (n = 7), 66.7% of grade III oligoastrocytomas (n = 6), 66.7% of glioblastomas with oligodendroglial component (n = 12), 0% of grade I astrocytomas (n = 13), 0% of grade II astrocytomas (n = 4), 0% of grade III astrocytomas (n = 12) and 2.5% of glioblastomas and gliosarcomas (n = 40).INA was expressed by 27(71.1%) of pure oligodendrogliomas(n=38) versus 17(17.2%) of no pureoligodentrogliomas(n=99), Chi-square was p < 10-4; Cramer’s V was 0.517; p <10-4, which show a very strong relationship.INA was expressed by 32(45.1%) of gliomas with IDH1 mutation (n=71) versus 12(18.2%) of gliomas without IDH1 mutation (n=66), Chi-square was p < 0.001; Cramer’s V was 0.288; p < 0.001, which show a very strong relationship. INA was expressed by 26(27.4%) of gliomas with P53 mutation (n=95) versus 18(42.9%) of gliomas without P53 mutation (n=42), Chi-square wasp=0.05 which show they were negatively correlated. INA was expressed by 30(50.0%) of gliomas with SYN expression (n=60) versus 14(18.2%) of gliomas without SYN expression (n=77), Chi-square was p < 10-4; Cramer’s V was 0.338; p < 10-4, which show a very strong relationship. INA was expressed by 12(27.3%) of gliomas with EGFR expression (n = 44) versus 32(34.%) of gliomas without EGFR expression (n=44), Chi-square was p=0.05 which show they were negatively correlated. Conclusion: INA expression is a fast, cheap and reliable diagnostic and prognostic marker, which helps identify patients of different prognostic groups in diffuse gliomas and should be used routinely in the pathologic diagnosis of glial tumours.Keywords: Glial tumours, Alpha-internecine, IDH1, P53, Synaptophysin, EGFR protein

Prediction of Response to Temozolomide in Low-Grade Glioma Patients Based on Tumor Size Dynamics and Genetic Characteristics

International audienceBoth molecular profiling of tumors and longitudinal tumor size data modeling are relevant strategies to predict cancer patients' response to treatment. Herein we propose a model of tumor growth inhibition integrating a tumor's genetic characteristics (p53 mutation and 1p/19q codeletion) that successfully describes the time course of tumor size in patients with low-grade gliomas treated with first-line temozolomide chemotherapy. The model captures potential tumor progression under chemotherapy by accounting for the emergence of tissue resistance to treatment following prolonged exposure to temozolomide. Using information on individual tumors' genetic characteristics, in addition to early tumor size measurements, the model was able to predict the duration and magnitude of response, especially in those patients in whom repeated assessment of tumor response was obtained during the first 3 months of treatment. Combining longitudinal tumor size quantitative modeling with a tumor''s genetic characterization appears as a promising strategy to personalize treatments in patients with low-grade gliomas. WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? þ First-line temozolomide is frequently used to treat low-grade gliomas (LGG), which are slow-growing brain tumors. The duration of response depends on genetic characteristics such as 1p/19q chromosomal codeletion, p53 mutation, and IDH mutations. However, up to now there are no means of predicting, at the individual level, the duration of the response to TMZ and its potential benefit for a given patient. • WHAT QUESTION DID THIS STUDY ADDRESS? þ The present study assessed whether combining longitudinal tumor size quantitative modeling with a tumor's genetic characterization could be an effective means of predicting the response to temozolomide at the individual level in LGG patients. • WHAT THIS STUDY ADDS TO OUR KNOWLEDGE þ For the first time, we developed a model of tumor growth inhibition integrating a tumor's genetic characteristics which successfully describes the time course of tumor size and captures potential tumor progression under chemotherapy in LGG patients treated with first-line temozolomide. The present study shows that using information on individual tumors' genetic characteristics, in addition to early tumor size measurements, it is possible to predict the duration and magnitude of response to temozolomide. • HOW THIS MIGHT CHANGE CLINICAL PHARMACOLOGY AND THERAPEUTICS þ Our model constitutes a rational tool to identify patients most likely to benefit from temozolomide and to optimize in these patients the duration of temozolomide therapy in order to ensure the longest duration of response to treatment. Response evaluation criteria such as RECIST—or RANO for brain tumors—are commonly used to assess response to anticancer treatments in clinical trials. 1,2 They assign a patient's response to one of four categories, ranging from " complete response " to " disease progression. " Yet, criticisms have been raised regarding the use of such categorical criteria in the drug development process, 3,4 and regulatory agencies have promoted the additional analysis of longitudinal tumor size measurements through the use of quantitative modeling. 5 Several mathematical models of tumor growth and response to treatment have been developed for this purpose. 6,7 These analyses have led to th

Alfa Internexin Expression in a Series of 137 Gliomas and its Correlation with Oligodentroglial Morphology IDH1, P53 SYN and EGFR Expression

Background: Distinguishing glial subtypes based on nuclear and cellular morphology alone is subjective,with significant interobserver variability, even among highly experienced neuropathologists. Genetic subtyping of a given histological phenotype and robust biomarkers has improved the diagnostic and prognostic assessment. Recently, IDH1 (more rarely IDH2) mutations have been found in nearly 40% of gliomas and strongly predict lower grade in histology and better outcomes. Aim: To evaluate if the expression of alpha-internexin (INA) can be used a reliable diagnostic, prognostic and cost-effective marker, a proneural gene-coding neurofilament interacting protein significantly correlated with oligodendroglial phenotype, 1p/19q codeletion as well as higher chemosensitivity and better prognosis to our study population. Material: We studied INA expression in 137gliomasand correlated it with pure oligodendroglial histology, IDH1, p53, EGFR and SYN expression by immunohistochemistry.Results: INA was expressed in 72.2% of grade II oligodendrogliomas (n = 22), 62.5% of grade III oligodendrogliomas (n = 16), 57.2% of grade II oligoastrocytomas (n = 7), 66.7% of grade III oligoastrocytomas (n = 6), 66.7% of glioblastomas with oligodendroglial component (n = 12), 0% of grade I astrocytomas (n = 13), 0% of grade II astrocytomas (n = 4), 0% of grade III astrocytomas (n = 12) and 2.5% of glioblastomas and gliosarcomas (n = 40).INA was expressed by 27(71.1%) of pure oligodendrogliomas(n=38) versus 17(17.2%) of no pureoligodentrogliomas(n=99), Chi-square was p < 10-4; Cramer’s V was 0.517; p <10-4, which show a very strong relationship.INA was expressed by 32(45.1%) of gliomas with IDH1 mutation (n=71) versus 12(18.2%) of gliomas without IDH1 mutation (n=66), Chi-square was p < 0.001; Cramer’s V was 0.288; p < 0.001, which show a very strong relationship. INA was expressed by 26(27.4%) of gliomas with P53 mutation (n=95) versus 18(42.9%) of gliomas without P53 mutation (n=42), Chi-square wasp=0.05 which show they were negatively correlated. INA was expressed by 30(50.0%) of gliomas with SYN expression (n=60) versus 14(18.2%) of gliomas without SYN expression (n=77), Chi-square was p < 10-4; Cramer’s V was 0.338; p < 10-4, which show a very strong relationship. INA was expressed by 12(27.3%) of gliomas with EGFR expression (n = 44) versus 32(34.%) of gliomas without EGFR expression (n=44), Chi-square was p=0.05 which show they were negatively correlated. Conclusion: INA expression is a fast, cheap and reliable diagnostic and prognostic marker, which helps identify patients of different prognostic groups in diffuse gliomas and should be used routinely in the pathologic diagnosis of glial tumours

Co-Deletion of Chromosome 1p/19q and IDH1/2 Mutation in Glioma Subsets of Brain Tumors in Chinese Patients

OBJECTIVE: To characterize co-deletion of chromosome 1p/19q and IDH1/2 mutation in Chinese brain tumor patients and to assess their associations with clinical features. METHODS: In a series of 528 patients with gliomas, pathological and radiological materials were reviewed. Pathological constituents of tumor subsets, incidences of 1p/19q co-deletion and IDH1/2 mutation in gliomas by regions and sides in the brain were analyzed. RESULTS: Overall, 1p and 19q was detected in 339 patients by FISH method while the sequence of IDH1/2 was determined in 280 patients. Gliomas of frontal, temporal and insular origin had significantly different pathological constituents of tumor subsets (P<0.001). Gliomas of frontal origin had significantly higher incidence of 1p/19q co-deletion (50.4%) and IDH1/2 mutation (73.5%) than those of non-frontal origin (27.0% and 48.5%, respectively) (P<0.001), while gliomas of temporal origin had significantly lower incidence of 1p/19q co-deletion (23.9%) and IDH1/2 mutation (41.7%) than those of non-temporal origin (39.9% and 63.2%, respectively) (P = 0.013 and P = 0.003, respectively). Subgroup analysis confirmed these findings in oligoastrocytic and oligodendroglial tumors, respectively. Although the difference of 1p/19q co-deletion was not statistically significant in temporal oligodendroglial tumors, the trend was marginally significant (P = 0.082). However, gliomas from different sides of the brain did not show significant different pathological constituents, incidences of 1p/19q co-deletion or IDH1/2 mutation. CONCLUSION: Preferential distribution of pathological subsets, 1p/19q co-deletion and IDH1/2 mutation were confirmed in some brain regions in Chinese glioma patients, implying their distinctive tumor genesis and predictive value for prognosis

The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is <it>fatty acid-binding protein 7 </it>(<it>FABP7)</it>, involved in lipid metabolism, gene regulation, cell growth and differentiation.</p> <p>Methods</p> <p>We studied the functional role of FABP7 in human melanoma cell lines and using immunohistochemistry analyzed its expression pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.</p> <p>Results</p> <p>FABP7 mRNA and protein level is down-regulated following treatment of melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down-regulation of FABP7 using siRNA decreased cell proliferation and invasion but did not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi, 71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear localization. FABP7 expression was associated with tumor thickness in superficial spreading melanoma (P = 0.021). In addition, we observed a trend for an association between FABP7 expression and Ki-67 score (P = 0.070) and shorter relapse-free survival (P = 0.069) in this group of patients.</p> <p>Conclusion</p> <p>Our data suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in cell proliferation and invasion <it>in vitro</it>, and may be associated with tumor progression in melanoma.</p

Management of Low-Grade Glioma

The optimal management of patients with low-grade glioma (LGG) is controversial. The controversy largely stems from the lack of well-designed clinical trials with adequate follow-up to account for the relatively long progression-free survival and overall survival of patients with LGG. Nonetheless, the literature increasingly suggests that expectant management is no longer optimal. Rather, there is mounting evidence supporting active management including consideration of surgical resection, radiotherapy, chemotherapy, molecular and histopathologic characterization, and use of modern imaging techniques for monitoring and prognostication. In particular, there is growing evidence favoring extensive surgical resection and increasing interest in the role of chemotherapy (especially temozolomide) in the management of these tumors. In this review, we critically analyze emerging trends in the literature with respect to management of LGG, with particular emphasis on reports published during the past year