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Romina Alkier, Jasmina Okičić, V. Milojica

Purpose – The purpose of this paper is to determine the key factors that influence the probability of tourists’ return intention to the Opatija Riviera. Methodology – A structured questionnaire with a 5 point Likert scale was used within this research. The authors used the descriptive statistics to determine the satisfaction with the destination attributes, and attitudes regarding the novelty of offer and possibility of future revisit. With the use of T-test a statistically significant difference was determined for the score for the accommodation capacities, natural resources and novelty. Correlation analysis was used to determine the association between accommodation, natural resources, cultural resources, novelty, and return intention. Logistic regression model was used to get a better understanding of the factors that may influence probability of tourists’ return intention. Findings – Results indicate high level of satisfaction of tourists with the accommodation offer and natural resources, while the results for cultural tourist resources were not up to expectations. The results for novelty are moderate and consistent with the results expressed about possible return intention to Opatija Riviera in the future, which indicates the need for significant improvements within the offer. The results of a logistic regression model determined that the best predictors for repeat visit of tourists are primarily accommodation services, followed by natural resources and finally novelty. Contribution – Based on the findings acquired within this paper the authors proposed the guidelines for tourist offer improvement with a goal of increasing the satisfaction of tourists and stimulating them to revisit Opatija Riviera in the future.

S. Vranić, W. Chamil Senarathne, P. Stafford, K. Poorman, B. Pockaj, Z. Gatalica

Supplemental Digital Content is available in the text. The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

Introduction Acute appendicitis (AA) is the most common surgical condition of the abdomen in children. The aim of this study was to analyse the possible use of the neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prediction of AA complications in children. Material and methods We included 170 AA patients under 15 years of age, who were divided into the following groups: Group 1 – non-operated patients with AA, and Group 2 – patients who underwent appendectomy. Based on pathologic grades of AA, Group 2 was subdivided into: Group A – phlegmonous, Group B – gangrenous, and Group C – perforated AA. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Results In Group 2 NLR was significantly higher than in Group 1 (5.5 (1.9–9.9) vs. 2.3 (1.2–3.7); p < 0.001). A significant difference in NLR was found between Group C and Group A (p < 0.001), and as well as between Group B and Group A (p = 0.001). The determined optimal cut-off value of NLR in differentiating Group 1 vs. Group 2 was ≥ 3.48 (p < 0.001). In differentiating Group A from Group C the optimal cut-off value of NLR was ≥ 5.61 (p < 0.001). Furthermore, optimal cut-off value of NLR in differentiating Group A from Group B was ≥ 5.45 (p = 0.001). Conclusions The obtained results suggest that NLR could be used as a simple and reliable test in the diagnosis and prediction of AA complications in children. However, to draw definite conclusions on the predictive power of NLR as a marker of AA large multicentric studies are required.

Benno Kallweit, P. Antonino, J. Jahic, T. Kuhn, P. Liggesmeyer

This paper presents a semi-automated approach for detecting conflicts and inconsistencies between architecture solutions. Inconsistencies occur when two or more architecture solutions rely on each other but cannot be satisfied, and conflicts when there are contradictions within one single decision specification, such as contradictory variable range and value. The proposed approach comprises a set of checks followed by transformations of architecture solutions specified according to a domain-specific-language, also created in the context of this work, into state machines. The semi-automated approach is implemented as a plugin for the MagicDraw modeling tool, and was evaluated in a project from the automotive domain.

F. Robertson, I. Esene, A. Kolias, Tariq Khan, Gail Rosseau, W. Gormley, Kee B. Park, M. Broekman et al.

Background Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. Methods The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018–January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. Results Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). Conclusions Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs.

D. Frauchiger, A. Tekari, R. D. May, E. Džafo, Samantha C W Chan, J. Stoyanov, A. Bertolo, Xingshuo Zhang et al.

Low back pain related to intervertebral disk (IVD) degeneration has a major socioeconomic impact on our aging society. Therefore, stem cell therapy to activate self-repair of the IVD remains an exciting treatment strategy. In this respect, tissue-specific progenitors may play a crucial role in IVD regeneration, as these cells are perfectly adapted to this niche. Such a rare progenitor cell population residing in the nucleus pulposus (NP) (NP progenitor cells [NPPCs]) was found positive for the angiopoietin-1 receptor (Tie2+), and was demonstrated to possess self-renewal capacity and in vitro multipotency. Here, we compared three sorting protocols; that is, fluorescence-activated cell sorting (FACS), magnetic-activated cell sorting (MACS), and a mesh-based label-free cell sorting system (pluriSelect), with respect to cell yield, potential to form colonies (colony-forming units), and in vitro functional differentiation assays for tripotency. The aim of this study was to demonstrate the efficiency of three widespread cell sorting methods for picking rare cells (<5%) and how these isolated cells then behave in downstream functional differentiation in adipogenesis, osteogenesis, and chondrogenesis. The cell yields among the isolation methods differed widely, with FACS presenting the highest yield (5.0% ± 4.0%), followed by MACS (1.6% ± 2.9%) and pluriSelect (1.1% ± 1.0%). The number of colonies formed was not significantly different between Tie2+ and Tie2− NPPCs. Only FACS was able to separate into two functionally different populations that showed trilineage multipotency, while MACS and pluriSelect failed to maintain a clear separation between Tie2+ and Tie2− populations in differentiation assays. To conclude, the isolation of NPPCs was possible with all three sorting methods, while FACS was the preferred technique for separation of functional Tie2+ cells. Impact Statement Tissue-specific progenitor cells such as nucleus pulposus progenitor cells of the IVD could become an ultimate cell source for tissue engineering strategies as these cells are presumably best adapted to the tissue's microenvironment. Fluorescence-activated cell sorting seemed to outcompete magnetic-activated cell sorting and pluriSelect concerning selecting a rare cell population from IVD tissue as could be demonstrated by improved cell yield and functional differentiation assays.

Salinity is one of the most important ecological problems that affect irrigated agriculture in the world. Increased soil salinity inhibits plant growth through osmotic and ionic stress, but can also decrease availability of certain micronutrients. Copper is an essential metal for normal plant growth and development that participates in numerous biochemical and physiological processes and it is an essential cofactor for many metalloproteins. Copper concentration in two commercial tomato cultivars (grafted and non-grafted) was investigated under different levels of elevated soil salinity. Soil with EC 9.1 dS m-1 led to the highest copper deficiency, approximately by 37% in the non-grafted and 25% in the grafted tomato plants. The effect of a grafting technique is considered as an environmentally friendly tool for overcoming soil salinity problem.

Bikramaditya Ghosh, E. Kozarević

This study delves into the herding and bubble detection in the volatility domain of a capital market underlying. Furthermore, it focuses on creating heuristics, so that common investors find it relatively easy to understand the state of the market volatility. Hence, it can be termed that this study is focused on the specific financial innovation regarding bubble and herding detection coupled with investor awareness. The traces of possible volatility bubble emerge when it is positioned against its own lags (both lag1 and lag2). The volatility trigger indicated clear traces of herding and an embedded parabola function. Continuous and repetitive parabola function hinted at a subtle presence of “fractals”. Firstly, the detrended fluctuation analysis has been used with its multifractal variant. Secondly, the regularized form of Hurst calculation and analysis have been used. Both tests reveal the traces of nascent bubble formation owing to prominent herding in CNX Nifty HFT environment. They also indicate a clear link with Hausdorff topological patterns. These patterns would help to create heuristics, enabling investors to be aware of possible bubble and herd situations.

T. Došlić, Ivica Martinjak, R. Škrekovski

We present a new class of totally positive Toeplitz matrices composed of recently introduced hyperfibonacci numbers of the r -th generation. As a consequence, we obtain that all sequences F n ( r ) of hyperfibonacci numbers of r -th generation are log-concave for r  ≥ 1 and large enough n .

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