Introduction: Rare diseases are becoming more and more important since awareness is increasing. There are a lot of initiatives to ensure access to orphan drugs intended to treat these diseases but due to high price patients have low access and policy makers and payers are struggling with costs and assuring patient access rights to the available medication. Aim: Objective of this study is to assess current situation regarding rare diseases in Bosnia and Herzegovina (BiH) and availability of orphan drugs. Four domains are examined: legislation and policy, diagnostics and research, patient organizations and reimbursement and availability of medicines for rare diseases. Results: There are official programs and legislation ground for rare diseases in both entities of BiH: Republic of Srpska (RS) and Federation of BiH (FBiH). Diagnostic and genetic counseling are available but only for few rare diseases. Patient organizations are formed and active but still without engagement in some of international organizations. There are no special reimbursement criteria for orphan medicines. Number of reimbursed medicines is significantly lower than those on ORPHANET list, 67 and 26 in RS and FBiH respectively. Huge difference in number of reimbursed medicines within the country entities may be consequence of counting method. Conclusion: Even thou rare diseases in BiH are recognized in countries official programs and documents, with patients having their organizations, much more have to be done in availability of medicines and diagnostics in the rare disease field. Insufficient funds are huge obstacle toward this goal. New methods of medicine evaluation are need and recommended in order of better availability.

We investigated multivoxel proton magnetic resonance spectroscopy (1H-MRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-grade glioma (LGG) and high-grade glioma (HGG). In total, 33 patients (HGG, 14; LGG, 9; and 10 MET) were included. 1H-MRS imaging (MRSI) data were assessed and neurochemical profiles for metabolites N-acetyl aspartate (NAA) + NAAG(NAA), Cr + PCr(total creatine, tCr), Glu + Gln(Glx), lactate (Lac), myo-inositol(Ins), GPC + PCho(total choline, tCho), and total lipids, and macromolecule (tMM) signals were estimated. Metabolites were reported as absolute concentrations or ratios to tCho or tCr levels. Voxels of interest in an MRSI matrix were labeled according to tissue. Logistic regression, receiver operating characteristic, and Kaplan–Meier survival analysis was performed. Across HGG, LGG, and MET, average Ins/tCho was shown to be prognostic for overall survival (OS): low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (log rank < 0.007). Lip/tCho and Ins/tCho combined showed 100% sensitivity and specificity for both HGG/LGG (P < .001) and LGG/MET (P < .001) measured in nonenhancing/contrast-enhancing lesional tissue. Combining tCr/tCho in perilesional edema with tCho/tCr and NAA/tCho from ipsilateral normal- appearing tissue yielded 100% sensitivity and 81.8% specificity (P < .002) for HGG/MET. Best single biomarker: Ins/tCho for HGG/LGG and total lipid/tCho for LGG/MET showed 100% sensitivity and 75% and 100% specificity, respectively. HGG/MET; NAA/tCho showed 75% sensitivity and 84.6% specificity. Multivoxel 1H-MRSI provides prognostic information for OS for HGG/LGG/MET and a multibiometric approach for differentiation may equal or outperform single biometrics.

Background: Oral dietary supplementation is becoming increasingly popular as an addition to classical approaches for the prevention and treatment of hemorrhoidal disease. Aim: To examine the effect of orally administrated alpha lipoic acid (ALA), known for its antioxidant and anti-inflammatory properties, in the treatment of patients with permanent symptoms of hemorrhoidal disease. Methods: Patients with second- and third-degree hemorrhoids (n = 100) were enrolled into a randomized, open label, single-center trial. The study group (n = 50) was treated with 200 mg of orally administered ALA once a day during the 12-week period, the control group (n = 50) did not receive any treatment. Results: There were no significant differences in demographics, diagnosis, or exposure to major risk factors between the study and placebo group at baseline. ALA significantly improved subjective efficacy variables, such as pain and discomfort (p < 0.01) as well as objective signs of the disease, such as bleeding (p < 0.01), in comparison to the control group. Furthermore, the 3-month treatment significantly reduced the number of patients with positive C-reactive protein (CRP) value (serum CRP > 5 mg/L) from 18% before to only 2% after the treatment (χ2 = 4.65; p < 0.01). Average leukocyte count has also been significantly reduced in the treatment group (p < 0.01) from 7.29 × 109/L before to 6.18 × 109/L after treatment. Conclusions: The obtained results indicate that ALA is effective in the treatment of second- and third-degree hemorrhoids. Larger, double-blind controlled trials are needed to confirm the results and to investigate optimal treatment regimens.

In this paper we consider a finite-horizon optimization problem with a distributed control policy. The local outputs are sent to a local controller in an intermittent fashion. As a consequence the controller has access to sensor information only if it is sent by the associated local scheduler or by neighboring controllers. We consider generalized event-triggered schedulers (which includes time-triggered schedulers as a special case, where time-instants define the events). This leads to an event-dependent information structure available at each local controller. As a result, the information structure changes, which potentially leads to a non-convex control design problem. For any event-triggered sensing topology, we give a necessary and sufficient condition for convexity of the optimal control problem, by using the quadratic invariance (QI) property. Furthermore, we provide an online algorithm that adapts the communication topology among the local controllers and guarantees a step-by-step QI, which translates to a global QI.

In this paper, we introduce the concept of student collegiality as a novel way to conceptualise student engagement in higher education-grounding our discussion in the evolving discourse of Students as Partners (SaP). We argue that student collegiality-a peer-to-peer discovery process-engages students in learning in a more authentic way than traditional pedagogical approaches and in the process supports their transition from higher education to professional working environments.

Introduction: Genetic polymorphism is associated with individual responses to medication and susceptibility to diseases, and it represents the basis for individualized medical treatment and drug genomics studies. Genetic variation at CYP2D6 is high, both among populations and among individuals in the same population. Aim: The aim of the study was to investigate the CYP2D6 gene duplication and the non-synonymous single-nucleotide polymorphisms (SNP) 100C>T in the CYP2D6 gene in members of the Bosnian population. Material and Methods: The blood samples were collected from 151 unrelated and healthy donors from Bosnian populations consisted of 94 females and 57 males. Duplex long-range PCR was used to determine whether individuals carrying CYP2D6 gene duplication. The resulting PCR product of 5.1 kb, containing all nine CYP2D6 exons, was used as template for detection of the CYP2D6 100C>T allele by nested PCR. Results: The CYP2D6 gene duplication frequency found in the Bosnian population (2.73%) was related to the frequencies of this allele in other Caucasians. The gene duplication is the result of inheritance of more than two copies of the fully functional CYP2D6 alleles. In contrast, the frequency of the CYP2D6 100C>T variant, with possibly damaging function, in the Bosnian population (15.56%) was significantly higher when compared with the other Caucasians but significantly lower when compared with Asians. Conclusion: CYP2D6 metabolizes many commonly prescribed drugs. Variations in the gene encoding this enzyme have been associated with individual differences in drug metabolism rates. The individuals with multiple CYP2D6 gene copies metabolize drugs more rapidly and therapeutic plasma levels will not be achieved at ordinary drug dosages. The non-synonymous coding SNP (100C>T) were predicted to have damaging effects on the protein function.

Abstract. In this paper, we consider the asymptotic behaviour of τ -Li coefficients for the wide class of L-functions that contains the Selberg class, the class of all automorphic L-functions, the Rankin-Selberg L-functions, as well as products of suitable shifts of the mentioned functions. We consider both archimedean and non-archimedean contribution to the τ -Li coefficients, both separately, and their joint contribution to the coefficients. We also derive the behavior of the coefficients in the case the τ/2-Riemann hypothesis holds, which is the generalization of the Riemann hypothesis for the class under consideration. Finally, we conclude with some examples and numerics.

Abstract Given are necessary conditions for a permutation polynomial to be the derivative of a planar mapping. These conditions are not sufficient and there might exist permutation polynomials which are not derivatives of some planar mapping satisfying these conditions. For the first time we show that there is a close connection between two seemingly unrelated structures, namely planar and complete mappings. It is shown that any planar mapping induces a sequence of complete mappings having some additional interesting properties. Furthermore, a class of almost planar mappings over extension fields is introduced having the property that its derivatives are permutations in most of the cases. This class of functions then induces many infinite classes of complete mappings (permutations) as well.

Abstract Automatic creation of school timetables is a complex problem when it involves defining specific constraints and requirements. This paper presents a domain-specific language called REDOSPLAT which supports such definitions in a readable format. REDOSPLAT can be used when timetable programs with a graphical user interface are limited or too cluttered to express specific domain features. It uses customised, readable notation instead of technically oriented data formats which are usually used in timetable problems. The desired timetabling requirements are defined using sentences whose syntax is close to the syntax of spoken language. This paper encompasses the entire language syntax and semantics, the way a sentence is transformed into data structures which describe timetabling requirements, and the way the obtained data structures are transformed into models needed for different problem-solving algorithms. For the latter, REDOSPLAT is using integer linear programming to resolve the timetabling problem.

Introduction: Socioeconomic changes have a significant impact on the health of the population. Socioeconomic development of society is one of the basic determinants of the health condition and needs of the individual and in the population as well. Aim: To explore the existence of differences in indicators of oral health status between the displaced persons and domicile population, considering the socioeconomic status (SES) of the respondents. Patients and Methods: A total of 310 people, aged 35-44 (mean 40.19 ± 3.60), were interviewed and examined, with 157 of them in a subsample of domicile inhabitants and other 153 respondents in displaced persons subsample. The SES of respondents was determined using a survey. After conducted examinations in study participants, determined results were recorded as dental status (DMFT Index), and periodontal status (CPI Index). Results: There was a significant difference in the mean value of caries existence between displaced persons of low and middle SES. In domicile inhabitants, there were no statistically significant differences in mean values of caries existence between the individuals with low and middle SES, while the differences existed between the individuals with low and high and between the middle and high SES. Domicile inhabitants with high SES had significantly less carious lesions than those with lower SES. Domicile inhabitants with high SES had significantly fewer extractions and more teeth with fillings. Conclusion: People with low SES have worse oral health status. Displacement and low socioeconomic status significantly influence the state of oral health.

Introduction: The carbohydrate antigen (CA 19-9) is a marker for pancreatic and colorectal carcinoma. In our study, we have investigated the level of CA 19-9 at 50 patients with benign and malign disease using three immunoassays. Methods: The COBAS e 601 (Roche) uses an ECLIA, Architect i2000 analyzer (Abbott) uses CMIA and VITROS 5600 uses integrated System Intellicheck Technology with cut off 0.0-37.0 U/mL for determination of CA 19-9. Results were with a statistical significance of p < 0.05. Results: Comparison of CA19-9 on COBAS with Architect show correlation coefficient R = 0.708. The results showed a regression line between immunoassay in patients with CA 19-9 treatment of y (Cobas) = 16.14 x (Architect) + 0.53. The comparison of CA19-9 on Architect and Cobas show correlation coefficient R = 0.709. The results showed regression line between immunoassay in patients with CA 19-9 treatment of y (Vitros) =–5.558 + 2.432 x (Architect) and correlation coefficient R = 0. 990. The mean concentration of CA 19-9 in the CMIA method was 41.49 U/mL, Intellicheck Technology was 103.45 U/mL and using ECLIA method was 47.25 U/mL at patients. Conclusions: Patients should be monitored on a single method to avoid differences in the results. The various immunoassay techniques for the detection of CA 19-9 tumor marker using different monoclonal antibodies, which leads to different results. Different antibodies recognize different parts of the molecule, and antigen heterogeneity may account in part for inter-method differences.

Abstract This paper provides insights into the informal economy of Bosnia and Herzegovina (BiH), a post--conflict transition economy in the Western Balkan region aspiring to became part of the European Union. After the introductory section and literature review, we introduce the economic outlook of BiH and then provide evidence estimating the size of the informal economy, which is identified to be around 30% over the last couple of years. As the size of the informal economy is high and persistent, this implies that current policy approaches are not efficient in tackling this economic challenge. To understand how the informal economy operates in practice, we use data from two different surveys to assess tax morality, undeclared work and the structure of the participants in the informal economy. In the next section, we supplement the study with ethnographic insights. In particular, we identify how participants in the informal economy use it for different purposes and with different motives. This includes reliance on the informal economy as a survival strategy for households, as a way to supplement insufficient formal income, to compensate for economic insecurity, or to decrease costs of formal business by using “envelope wage” practices, but equally importantly to overcome formal institutional rigidities linked to current contradictory laws. Still, we find indications that the growth of informal business is converging to formalisation, as informality at some stages of business development becomes a burden to higher entrepreneurial growth aspirations.

Thymoquinone (TQ), a natural compound with antimicrobial and antitumor activity, was used as the starting molecule for the preparation of 3-aminothymoquinone (ATQ) from which ten novel benzoxazole derivatives were prepared and characterized by elemental analysis, IR spectroscopy, mass spectrometry and NMR (1H, 13C) spectroscopy in solution. The crystal structure of 4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazole-5-ol (1a) has been determined by X-ray diffraction. All compounds were tested for their antibacterial, antifungal and antitumor activities. TQ and ATQ showed better antibacterial activity against tested Gram-positive and Gram-negative bacterial strains than benzoxazoles. ATQ had the most potent antifungal effect against Candida albicans, Saccharomyces cerevisiae and Aspergillus brasiliensis. Three benzoxazole derivatives and ATQ showed the highest antitumor activities. The most potent was 2-(4-fluorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1f). Western blot analyses have shown that this compound inhibited phosphorylation of protein kinase B (Akt) and Insulin-like Growth Factor-1 Receptor (IGF1R β) in HeLa and HepG2 cells. The least toxic compound against normal fibroblast cells, which maintains similar antitumor activities as TQ, was 2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazole-5-ol (1e). Docking studies indicated that 1e and 1f have significant effects against selected receptors playing important roles in tumour survival.

Objedinjavanje građe u fondovima NUBBiH o kulturnohistorijskoj zaostavštini Silvija Strahimira Kranjčevića rezultat je realizacije projekta Nacionalne i univerzitetske biblioteke Bosne i Hercegovine (NUBBiH), finansiran od strane Ministarstva za obrazovanje, nauku i mlade Kantona Sarajevo. Predmet istraživanja bila je građa iz fondova Specijalnih zbirki, Stare periodike i novije literature, monografije i članci, koji se čuvaju u Redovnom fondu NUBBiH. Konačni rezultat istraživanja je bibliografija koja sadrži 394 jedinice. Po završetku projekta izdvojena je i skenirana sva popisana građa o Silviju Strahimiru Kranjčeviću i dostupna je u digitalnoj formi na odjeljenjima u kojima se nalazi.

Received: 30 September 2017 / Accepted: 25 April 2018 Abstract: In this paper a damping rate analysis was performed on the cantilever beam and loaded with an additional mass at the free end. The experimentally obtained results for bending damping vibration of the cantilever have been analyzed. The analysis gives the dependence of the damping factor, measured as the relation of the two adjacent amplitudes, from the moment of inertia, all in a non-dimensional form. It was found that there is an influence of additional mass on the internal damping coefficient for different inertia moment of the cantilever.