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Castalagin, a nonahydroxytriphenoyl-bearing C-glucosidic ellagitannin, manifested a marked virucidal effect on HSV-1.

Two rational mathematical models for synthesis of mechanisms with conjugate disk cams translating with offset roller follower are derived from the equivalent four-bar linkage theory. They are linear and comparable in their relative simplicity, applicability and principle accuracy. The re-sults obtained from one model are verified by another, so any errors are excluded. The conditions for the same profile of the double-lobed cam are obtained. The models are demonstrating by means of example for the cam profile synthesis.

This review describes the contemporary state of research for antivirals effective against flaviviruses, especially focusing on inhibitors of the pestivirus causative agent of bovine viral diarrhoea virus. We highlight cycluridine, an originally synthesized Mannich’s base [a tetrahydro-2(1H)-pyrimidinones derivative], as a highly effective antiviral possessing a strong inhibitory effect on bovine viral diarrhoea virus replication. Cycluridine was active against replication of a wide variety of bovine viral diarrhoea virus strains in cell cultures. The drug-sensitive period in the bovine viral diarrhoea virus replication cycle included the latent period and the exponential phase; a 90-min delay in the peak of viral RNA synthesis was observed. Cycluridine administered orally manifested a pronounced protective effect in calves with natural mucosal disease/viral diarrhoea and calves experimentally infected with bovine viral diarrhoea virus. Its magnitude of activity and selectivity places cycluridine in the lead among all known substances with anti- bovine viral diarrhoea virus activity. Additionally, cycluridine applied subcutaneously showed anti-tick-born encephalitis virus activity, manifesting a marked protective effect in mice infected with tick-born encephalitis virus. Cycluridine could be a prospective antiviral in veterinary and medical practice for the treatment of bovine viral diarrhoea virus and other flavivirus infections.

Titanium (Ti) is a non-essential metal element. TiO2 is used predominantly in the form of micro and nanoparticles in consumer products, including cosmetics and food. Because of its excellent biocompatibility, the trade-pure titan and its alloys are widely used as an alternative to certain metals in invasive medicine, surgery, dental medicine. Contemporary data concerning the sources of exposure to titanium, immune reactions to Ti alloys, current knowledge and perspectives of diagnosis of sensitization or allergic reactions to titanium are discussed. Conclusion: TiO2 is much more stable than pure Ti and alloys used in the implants, that should be taken into account when conducting research and analysing the results. The evidence of possible toxic effects is insufficient. It is difficult to assess the frequency of Ti allergy due to the uncertainty of diagnostic methods, but it is believed that it is very low. This is supported by the evidence that Ti and TiO2 (often as NP) doesn’t penetrate through the healthy skin. Skin patch testing with currently available formulations of Ti and TiO2 has no significant value in clinical practice, and currently, it is assumed that there is no reliable method for diagnosis Ti allergy. The functional analysis of cytokine release and investigation of genetic characteristics could be useful for individual risk assessment in dental implantology. Such studies may also help to investigate separately early and late implant loss, as well as to develop new diagnostic tools.

Пациентите с хронични чернодробни заболявания обикновено са с влошено орално здраве. Съществуват множество орални симптоми и находки в устната кухина, които могат да бъдат отражение и на общото здравословно състояние на пациентите. Денталното лечение на чернодробно болните преди трансплантацията и отстраняването на всички потенциални огнища на инфекция е задължителна рутинна процедура в част от специализираните центровете за лечение на този контингент болни по света.Препоръчва се преди органната трансплантация болните да бъдат прегледани и лекувани от дентални лекари, тъй като нелекуваните орални заболявания (вкл. дентални проблеми) могат да бъдат причина за инфекции и сепсис и да доведат до редица усложнения при трансплантираните пациенти, дори и до летален изход. Поради тези причини вниманието на медиците и на лекарите по дентална медицина е насочено към оралното здраве на пациентите с хронични чернодробни заболявания и кандидатите за чернодробна трансплантация, работейки в мултидисциплинарни екипи с основни задачи: успешна трансплантация, предотвратяване на възможните усложнения и подобряване на качеството на живот. Чернодробната трансплантация в България вече е рутинна терапевтична процедура. Продължават очакванията и търсенията да се създават по-съвременни и подобрени протоколи при извършването ѝ. Липсват специфични протоколи за диагностика и лечение на оралните и денталните заболявания на този контингент пациенти в нашата страна. В кол, The patients with chronic liver disease usually have poor oral health. There are numerous oral symptoms and findings in the oral cavity that may also reflect the general health of the patients. Dental treatment of the patients with liver disease before transplantation, and removal of all potential foci of infection is a mandatory routine procedure in some of the specialized centers for the treatment of this group of patients worldwide. It is recommended that the patients should be examined and treated by dental specialists before organ transplantation, as untreated oral diseases (including dental problems) can cause infections and sepsis and lead to a number of complications in the transplanted patients, and can even lead to death.Fo r these reasons, the attention of the medical doctors and the dentists should be focused on the oral health of the patients with chronic liver disease and applicants for liver transplantation, working in multidisciplinary teams with prime aims: successful transplantation, prevention of possible complications, and improving quality of life of these patients.Liver transplantation in Bulgaria is already a routine therapeutic procedure. Expectations and researches continue to create more up-to-date and improved protocols in its execution. There are no specific protocols for diagnostics and treatment of the oral and dental diseases of this group of patients in our country. In collaboration with the Military-Medical Hospital Sofia and their Transplant

International audience; Background: We developed a new approach for the treatment of enterovirus infections, the consecutive alternating administration (CAA) of a combination of enterovirus inhibitors. On the model of coxsackievirus B1 (CVB1) in mice, two phenomena were observed: absence of drug resistance and increased susceptibility to the antivirals. This study aims to clarify the genetic basis of these phenomena. Methods: Brain samples from CVB1-infected mice subjected to a CAA course with the combination pleconaril/MDL-860/oxoglaucine were used for viral RNA extraction and next generation sequencing. In parallel, samples from monotherapeutic courses of the three substances included in the combination were studied. Whole genome sequence analysis was carried out on all samples. Results: Samples of pleconaril monotherapy showed mutations in 5 0 untranslated region, VP3, 2C, 3C and 2A regions of viral RNA, translated in amino acid substitution of the 2A protein. The MDL-860 course induced changes in CVB1 RNA in the VP3 and 2C regions. The oxoglaucine monotherapy samples showed RNA mutation and amino acid substitution in the VP1 region and nucleotide substitution in the 3D region. In the specimens taken from mice subjected to the CAA course with pleconaril/MDL-860/oxoglaucine, the following RNA mutations were established: 5 0 untranslated region, 2A, and 2B, and amino acids substitutions in VP3 and 2A, which differ from those mentioned above. These changes could be the reason for the prevention of drug resistance development and also to be considered as the basis for the phenomenon of increased drug susceptibility. Conclusions: The results reveal that the high anti-enteroviral efficacy of the CAA course is substantiated by the appearance of specific changes in the viral genome.

Herein, we report design and synthesis of series of adamantane derivatives containing modified peptides with thiazol moiety. New compounds were synthesized in solution using TBTU (2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate) as coupling agent. All derivatives were obtained with good yields. The antiviral activity of newly synthesized compounds against influenza virus H1N1 is studied. Cytotoxicity assay for determination of CC50 were done and IC50 values were calculated. The rimantadine analogue with thiazole ring Gly-Thz-rimantadine showed good activity against influenza virus A/Hongkong/68 with IC50 = 0.11 μg/mL and CC50 = 50 μg/mL. In addition, antimicrobial and antifungal activity against model strains of gram positive (Bacillus cereus), gram negative (Escherichia coli) microorganisms and fungi strain Yarrowia lipolytica 3344 were investigated. The compounds Gly-Thz-rimantadine with good antiviral activity also showed very good antifungal activity in two different concentrations.

We present the results of the numerical hindcast of the storm surges affecting the Bulgarian Black Sea coast during the period 1979-2020, using atmospheric data from the ERA5 reanalysis. The aim of the study is to evaluate the changes in the surge intensity and frequency during the period. The highest identified surges in the hindcast output are the surges of February 1979, January 1981 and February 2012- the surge of 2012 is the highest, while the surge of 1979 was found to be the longest and the most energetic event. We found no statistically significant inter annual change in the number, total duration and the introduced index characterizing the total energy of the surges above 60cm or 80cm was found. The total annual number of events above 40cm is with increasing trend which is statistically significant, but the total duration of events above 40cm does not show statistically significant trend- we observe more frequent but shorter events in the range 40-60cm during the last decade., Proceeding of 1st International Conference on Environmental Protection and Disaster RISKs, 2020, p. 311-318

The study presents a reconstruction of the Western Black Sea wave climate based on a numerical hindcast using the SWAN wave model and ERA5 input data. While there are many wave hindcasts reconstructing the Black Sea wave climate, based on various atmospheric reanalysis projects, the present work is the first based on the state of art ERA5 reanalysis. We focus on the storminess affecting the Bulgarian coast. The storminess in the recent decade (2010-2019) was found to be the highest compared to the previous 3 decades covered by the reanalysis (while the previous 2000-2009 is with the lowest), but the trends in the storm proxies used in the study are not statistically significant. This confirms the conclusions of other studies that the wave climate of the Western Black Sea is steady., Proceeding of 1st International Conference on Environmental Protection and Disaster RISKs, 2020, p. 302-310

Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of.The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant.The crude aqueous ethanolic extract from aerial parts of.The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of.The crude extract from aerial parts of the medicinal plant.

International audience; Objective: The accuracy of phase-contrast magnetic resonance imaging (PC-MRI) measurement is investigated using a computational fluid dynamics (CFD) model with the objective to determine the magnitude of the flow underestimation due to turbulence behind a narrowed valve in a phantom experiment. Materials and Methods: An acrylic stationary flow phantom is used with three insertable plates mimicking aortic valvular stenoses of varying degrees. Positive and negative horizontal fluxes are measured at equidistant slices using standard PC-MRI sequences by 1.5T and 3T systems. The CFD model is based on the 3D lattice Boltzmann method (LBM). The experimental and simulated data are compared using the Bland-Altman-derived limits of agreement. Based on the LBM results, the turbulence is quantified and confronted with the level of flow underestimation. Results: LBM gives comparable results to PC-MRI for valves up to moderate stenosis on both field strengths. The flow magnitude through a severely stenotic valve was underestimated due to signal void in the regions of turbulent flow behind the valve, consistently with the level of quantified turbulence intensity.Discussion: Flow measured by PC-MRI is affected by noise and turbulence. LBM can simulate turbulent flow efficiently and accurately, it has therefore the potential to improve clinical interpretation of PC-MRI.

This paper represents basic features of a modern e-learning system that aims to increase efficiency of teaching process. Like the polygraph (known also as a lie detector), system collects data about body parameters of individual learners, responding to their psychological state and takes real time decisions about best way that learning content should be presented to them according to their learning modality. Following the same principles, examination and evaluation processes can be also improved under some conditions. Advanced low-energy sensor network technology is also described as a backbone on which is based body data collection. The purposed system is flexible and suitable for both small and large groups of learners and can be built independently or easy integrated as an extension of existing e-learning system. The main limit of the purposed system is that it is appropriate mainly for the attendance learning forms. As an extra benefit, the sensors may detect if any learner has abnormal body functions and may alert about his health hazards.

The purpose of this paper is to investigate the graph-based representation of the data required for the vector space model (VSM) and PMI (pointwise mutual information)-enriched VSM used for text mining (e.g. text classification). The transformation of a dataset containing free text reviews for online stores in a graph-based form is described and its format that allows to be used by Neo4j graph database management system is proposed. Queries for retrieving the data required for training text mining models are considered; the steps and the actions for their modification when receiving new data are specified. The advantages of the proposed graph-based representation in regard to the maintenance and the extraction of current data needed for retraining data mining models are summarized, in order to prevent loss of performance of results from the execution of the respective data mining task.

Studies on factors influencing the physical, mental, and health status of humans use different complex indicators to measure the impact of these factors. However, in those indicators there always features a component to account for the expected change in life expectancy. Most often this is the average life expectancy. The present work proposes the use of alternative indicators that can give a more objective view of the impact of the relevant factor. They are compatible with the methodology for calculating average life expectancy and do not require additional data.

This article reviews some of the available models for controlling Human Centric Lighting systems. The author develops and adapts one of the models, so that it can be applied in design HCL systems in practice. The proposed new HCL control model take into account summer and winter daylight conditions and the effect of the aging eye on light perception. It also shows the necessary curve adjustments for different age groups in practice.

comparison of the classical approach using a harmonic signal with the approach of a periodic square wave signal in the first (main) harmonic of the calibration voltage of the electrical power quality analyzers is suggested. The results presented using both approaches for calibrating a Fluke 435 power quality analyzer through a Metrix CX1651 calibrator, provide a quantitative estimate of the degree of equivalence of calibration by both approaches. Evaluation and comparison of the obtained experimental results shows applicability of the approach with a periodic square wave signal of the calibration of power quality analyzers by harmonic voltage in the metrological practice.

Technologies using Unmanned Aerial Vehicles (UAVs) have been the subject of research for many years now. They are increasingly used in a number of public and private projects. UAVs with their mobility and ability to fly at different altitudes can compensate for some shortcomings in the wireless sensor network and offer an alternative approach to data harvesting. With their help, it is easy to allow spatial research of different areas/spaces. This is particularly important in the study of air pollution, which changes sharply even over relatively short distances in the horizontal and vertical directions. In the present study is presented a research of possibilities for application of a new instrument for studying the air quality at different altitudes, which is accessible to a wide range of users. The approach is based on using cheap UAVs and low-cost air quality sensors. This paper shows the relevance of a customized, off the shelf UAV equipped with mobile monitoring devices as an effective, versatile, and unconventional means to collect three-dimensional air pollutant concentration data.

In the present paper algorithms for creating mathematical models for spectral luminance of Tunable White luminaires are suggested. The models include some levels, which contain models of the spectral luminance for the specific correlated color temperature, based on the specific Gaussian functions; luminance models for other color temperatures in different work hypothesis and spectral luminance models for the entire color temperature control range. The accuracy of the proposed model is compared with the data from experimental research.

The article examines an experimental installation with a Human Centric Lighting illuminator to find out if new technologies such as Tunable White and Dali Device Type 8 meet the requirements for accurate and smooth change in the radiated color temperature of the illuminator. To this end, a number of real-time measurements have been carried out and analyzed. The measurement results are summarized in the graphs for the illuminator investigated

В дисертационния труд са разгледани специфични проблеми и особености на калибрирането и проверката на анализатори на електрическа енергия. Представени са актуални данни за текущото състояние на калибрирането на анализатори на електрическа енергия в Р. България, като са посочени изискванията към съответните лаборатории. Анализирани се възможностите за приложение на съвременните виртуални технологии за автоматизиране на дейностите по калибриране и проверка на анализатори на електрическа енергия. Анализирани са възможностите за използване на периодичен правоъгълен сигнал при калибриране на анализатори на електрическа енергия. Проведени са съответни метрологични анализи при калибриране по хармоници и по коефициент на нелинейни изкривявания. Като резултат е предложен подход за калибриране по хармоници и по коефициент на нелинейни изкривявания чрез използване на периодичен двуполярен правоъгълен сигнал, който е алтернатива на класическия подход с генериране на самостоятелни хармонични сигнали. Предложени са математически модели за изчисляване на действителната стойност на измерваната величина и нейната неопределеност при калибриране на анализатор на електрическа енергия за: напрежение, ток, мощност (активна, реактивна, пълна), cosφ, честота, хармоник (на напрежението и на тока), коефициент на нелинейни изкривявания (на напрежението и на тока) и фактор на мощността. Разработени са математическите модели, използвани при проверка на анализатори на електрическа енергия за: хармоник на In the dissertation work specific problems and features of the calibration and the verification of electrical energy analyzers are examined. Actual data on the current state of the calibration of electricity analyzers in the Republic of Bulgaria, and the requirements for the respective laboratories are presented. The possibilities of applying modern virtual technologies for the automation of the calibration and the verification activities of electricity analyzers are analyzed. The possibilities of using a periodic squarewave signal for the calibration of electricity analyzers are discussed. Appropriate metrological analyzes are performed concerning the harmonics calibration and the total harmonic distortion. As a result a calibration approach is developed based on harmonics and the total harmonic distortion coefficient using a periodic bipolar squarewave signal, which is an alternative to the classic approach of generating standalone harmonic signals. Mathematical models are proposed for calculating the actual value of the measured variable and its uncertainty in the calibration of electric energy analyzer for: voltage, current, power (active, reactive, full), cosφ, frequency, harmonics (of voltage and current), total harmonic distortion (of voltage and current) and power factor. Mathematical models used for verification of the electrical energy analyzers for: harmonics of voltage and total harmonic distortion coefficient of voltage based on periodic bipolar squarewave sign

Slavic speaking populations are the most numerous Indo-European ethnolinguistic group in Europe. They show great variety and fall into three groups: West, East and South Slavic populations. In order to contribute to the understanding of the correlation between linguistic and genetic affiliation of Slavic populations, we have analyzed for the first time their matrilineal and patrilineal relationships and we have also illustrated their position in the European uniparental genetic landscape. For the purpose, we have collected previously published data for the frequencies of mitochondrial DNA (mtDNA) and Y-chromosome haplogroups in Slavic and other European populations and compared them by Principal Component Analysis (PCA). In the inter-Slavic population comparisons, West and East Slavs are in a closer position, whereas South Slavic populations are rather grouped on their own. In the European context, South Slavic populations are positioned more close to neighboring Balkan non-Slavic and North Italian populations, than to other Slavic populations. When considering the uniparental diversity of Slavic speaking populations, one should also take into account the prevalence of Y-chromosome haplogroup N among East Slavs (comprising almost half of the paternal gene pool in instances), which is almost absent among the other groups (not exceeding 2% - 3%). In conclusion, the data in the present study point that West-East and South Slavic speaking populations, behave as separate groups based on their uniparental genetic structure, which shows that they do not share substantial common genetic ancestry and that there is great genetic variety in the Slavic linguistic unity.

Various metal phthalocyanines have been studied for their capacity for photodynamic effects on viruses. Two newly synthesized water-soluble phthalocyanine Zn(II) complexes with different charges, cationic methylpyridyloxy-substituted Zn(II)- phthalocyanine (ZnPcMe) and anionic sulfophenoxy-substituted Zn(II)-phthalocyanine (ZnPcS), were used for photoinactivation of two DNA-containing enveloped viruses (herpes simplex virus type 1 and vaccinia virus), two RNA-containing enveloped viruses (bovine viral diarrhea virus and Newcastle disease virus) and two nude viruses (the enterovirus Coxsackie B1, a RNA-containing virus, and human adenovirus 5, a DNA virus). These two differently charged phthalocyanine complexes showed an identical marked virucidal effect against herpes simplex virus type 1, which was one and the same at an irradiation lasting 5 or 20 min (Δlog=3.0 and 4.0, respectively). Towards vaccinia virus this effect was lower, Δlog=1.8 under the effect of ZnPcMe and 2.0 for ZnPcS. Bovine viral diarrhea virus manifested a moderate sensitivity to ZnPcMe (Δlog=1.8) and a pronounced one to ZnPcS at 5- and 20-min irradiation (Δlog=5.8 and 5.3, respectively). The complexes were unable to inactivate Newcastle disease virus, Coxsackievirus B1 and human adenovirus type 5.

The technical process has no associativity from the design area to the machine tool. In the chipping area, we need for an essential and continuous optimization in the whole process data’s from the machine tool. If we habe the possibility to optimize the components on design area, then we improve the complete process from the customer order entry to the delivery. Based on this information, it’s possible to reduce the time to market. On technical level, we have a functional revolution based on new workflows, processes to reduce the effort in the planning process, the product costs and manufacturing costs. The change process is also affected by the worflow from the production environment to the planning area.The design department defines approximately 70% of the product cost [Heimsoth 2006] - by modern connection technology it’s possible to receive in the CAD-system resource information of the production to optimize the whole process. So, it's helpful to derive preliminary cost estimation, based on 3D analytics which results based on the optimized technological data's. A manufacturable design is the basis for an optimized total process - the work plan for the ERP system can be generated already, too. It is also ensured that parts which have been designed under using analysis would be easy to produce.Based on the 3D-CAD-models the NC program can be created via feature-oriented automated rules (dependence of the CAM programming system), so that NC programs for alternative machines can be derived. This is necessary that we obtained the higher flexibility in production and reduction on process times.Based on machine signals, we send back the information’s over the machine connectors to the data-analytics database. So, it's implemented a holistic approach in the field of logistics, as well as in the technical field. With PDCA (continuous improvement process) it's ensured a steady optimization.The effects on real time data are implemented in the technical area within the reporting, interfaces and visualization. The decision-making process shows the importance of employees in the total chain.The benefits based on the realization of the Karlsruhe Institute of Technology (KIT) - Institute for Information Management in Engineering (IMI).

The classic SEAr mechanism of electrophilic aromatic substitution (EAS) reactions described in textbooks, monographs, and reviews comprises the obligatory formation of arenium ion intermediates (σ complexes) in a two-stage process. Our findings from several studies of EAS reactions challenge the generality of this mechanistic paradigm. This Account focuses on recent computational and experimental results for three types of EAS reactions: halogenation with molecular chlorine and bromine, nitration by mixed acid (mixture of nitric and sulfuric acids), and sulfonation with SO3. Our combined computational and experimental investigation of the chlorination of anisole with molecular chlorine in CCl4 found that addition-elimination pathways compete with the direct substitution processes. Detailed NMR investigation of the course of experimental anisole chlorination at varying temperatures revealed the formation of addition byproducts. Moreover, in the absence of Lewis acid catalysis, the direct halogenation processes do not involve arenium ion intermediates but instead proceed via concerted single transition states. We also obtained analogous results for the chlorination and bromination of several arenes in nonpolar solvents. We explored by theoretical computations and experimental spectroscopic studies the classic reaction of benzene nitration by mixed acid. The structure of the first intermediate in this process has been a subject of contradicting views. We have reported clear experimental UV/vis spectroscopic evidence for the formation of the first intermediate in this reaction. Our broader theoretical modeling of the process considers the effects of the medium as a bulk solvent but also the specific interactions of a H2SO4 solvent molecule with intermediates and transition states along the reaction path. In harmony with the obtained spectroscopic data, our computational results reveal that the structure of the initial π complex precludes the possibility of electronic charge transfer from the benzene π system to the nitronium unit. In contrast to usual interpretations, our computational results provide compelling evidence that in nonpolar, noncomplexing media and in the absence of catalysts, the mechanism of aromatic sulfonation with sulfur trioxide is concerted and does not involve the conventional σ-complex (Wheland) intermediates. Stable under such conditions, (SO3)2 dimers react with benzene much more readily than monomeric sulfur trioxide. In polar (complexing) media, the reaction follows the classic two-stage SEAr mechanism. Still, the rate-controlling transition state involves two SO3 molecules. The reactivity and regioselectivity in EAS reactions that follow the classic mechanistic scheme are quantified using a theoretically evaluated quantity, the electrophile affinity (Eα), which measures the stabilization energy associated with the formation of arenium ions. Examples of applications are provided.

Resume Cet article etudie comment le cadre legislatif bulgare aborde le fonctionnement de l’administration, dans le contexte particulier d’une societe en phase de transition politico-economique. Il s’appuie sur l’etude des pouvoirs discretionnaires attribues a l’administration en matiere de delivrance d’autorisations d’activite economique. Il met en avant a la fois les imperatifs d’encadrement de ce pouvoir et ceux de simplification des procedures liees a son exercice.

This paper presents an adapted method for tracking camera motion in the visualization of augmented reality. A tracking algorithm based on significant points and descriptors without the use of optical flow is described. The tracking module is written in C++. Experiments have been carried out of the precision of the system using the camera motion-tracking module created.

The article aims to represent a general overview of the prototype web-mapping interactive system SatWebMare for the Bulgarian coastal zone. The interactive system is designed to provide through geo-portal innovative products and services for integrated coastal zone management. The web-mapping system combines geo-databases from different sources such as satellite imagery, maps, vector layers and other datasets. The content of the SatWebMare Geo-Portal is briefly outlined. The web-interface system will provide access to applications and products with an improved spatial and temporal resolution for three areas of interest - sea waves, natural hazards and geomagnetism in the Area of Interest (AOI). The web-mapping system is developing based on the free and open-source software, OGS standards and following the EU INSPIRE Directive recommendations. Once the prototype system is fully developed, it will enable to provide access to value-added products and services that are useful to ministries, agencies, local authorities and other stakeholders in support of the decision making.

Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678