Manufacturers of self-driving cars need to significantly improve the safety of their products before the series of such cars are deployed in everyday use. A large number of architecture proposals for Automated Driving Systems (ADS) are aiming at addressing the challenge of safety. These solutions typically define redundancy schemes and quite commonly include self-checking pair structures, e.g., commander/monitor approaches. In such structures, the problem of false positive failure detections arises, i.e., the monitor may falsely classify the output of the commander as being faulty. In this paper, we review an ADS architecture for fully automated driving and propose a concept to remove false positives in a systematic way. We formalize our proposal in an abstract model and prove the absence of false positives by-means of k-induction. A reference to a technical report is given that contains a detailed discussion of the proof procedure.

We show a case of endophthalmitis presenting 7 weeks after intravitreal aflibercept injection. An unusual species of viridans streptococci, S. intermedius, was isolated. The case highlights the need to consider infection even in cases of very delayed-onset postinjection inflammation, and the potential wide variability in severity of Streptococcus viridans endophthalmitis. Purpose: Endophthalmitis following intravitreal anti–vascular endothelial growth factor injections is frequently caused by Streptococcus viridans organisms and tends to be aggressive. Herein, we present a case of postinjection Streptococcus viridans endophthalmitis presenting in an atypically delayed fashion with good visual outcome. Methods: Single clinical case report. Results: A 91-year-old woman treated with aflibercept for exudative age-related macular degeneration of the left eye presented to the emergency department with mild pain and visual acuity decline to counting fingers, pigmented anterior chamber cells and vitreous haze 7 weeks after her most recent intravitreal injection. She had no symptoms of systemic infection. The presumptive diagnosis initially was vitreous hemorrhage. Over 10 days of observation, she developed worsening pain and vitritis suggestive of endophthalmitis, leading us to perform vitrectomy with intravitreal vancomycin and ceftazidime. Vitreous biopsy was culture positive for Streptococcus intermedius, a type of viridans streptococcus typically associated with head and neck abscesses. The infection resolved and the patient's visual acuity returned to her baseline of 20/100, with no recurrence of infection after 4 months of follow-up. Conclussion: The virulence of viridans streptococci capable of producing postinjection endophthalmitis may vary widely. Infection ought to be suspected even in cases of delayed-onset intraocular inflammation.

Rad predstavlja javne, građanske apoteke koje su otvorene u Sarajevu u periodu austrougarske vladavine. Uspostavljanjem austrougarske uprave uređuje se apotekarska djelatnost i počinje otvaranje većeg broja javnih, građanskih apoteka. Koncesije za otvaranje apoteke većinom su dobijali stranci, jer domaćih apotekara nije bilo. Prva moderna apoteka u ovom periodu je otvorena 1878, a posljednja 1913. godine. U periodu 1898–1918. u gradu su otvorene samo dvije nove apoteke, a tokom četrdeset godina austrougarske vladavine radilo ih je ukupno sedam. Apoteke su često reklamirane u raznim publikacijama kao dobro snabdjevene svim potrebnim lijekovima i drugim proizvodima, kao što su kozmetika, pića, fotografski pribor. Apotekari su svojim radom doprinijeli unapređenju zdravstvene zaštite u gradu, kao i građanskoj kulturi i opštem razvoju društva zajedno sa svojim savremenicima.

Quality of measurement results and their accuracy in not neccessary to be high in conventional systems, approximate results are enough to know exactly what happens in the system. However, with increased penetration of renewable sources in the grid, need for high quality and precise measurements has risen. In order to have precise information about power quality, good knowledge of the behaviour of power quality analyzers is needed. Good knowledge can only be obtained by calibration of those meters. This paper describes start of development of a fully traceable power quality reference setup for the calibration of power quality analyzers based on digital sampling of voltage/current signals, and shown preliminary results.

Juvenile systemic sclerosis (JSSc) is a rare disease of childhood and currently no international consensus exists with regard to its assessment and treatment. This SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative, based on expert opinion informed by the best available evidence, provides recommendations for the assessment and treatment of patients with JSSc with a view to improving their outcome. Experts focused attention not only on the skin assessment but also on the early signs of internal organ involvement whose proper treatment can significantly affect the long-term outcome. A score for disease severity is proposed in order to perform a structured assessment of outcome over time but a validation in a wider patient population is recommended. Finally, a stepwise treatment approach is proposed in order to unify the standard of care throughout Europe with the aim to reduce morbidity and mortality in this disease.

This study attempted to evaluate the efficiency of zeolite and pyrophyllite ore materials in reducing the mobility of heavy metals in soil near the lignite mining dumps, and consequently in their availability for plants. Extraction of pseudo-total and available forms of heavy metals from soil samples was performed by using aqua regia and ethylenediaminetetraacetic acid, respectively. Concentrations of heavy metals in soil and plant samples were determined by atomic absorption spectrophotometry. The results of this study illustrate that application of zeolite and pyrophyllite could be a suitable technique to reduce heavy metals availability in soils. Zeolite treatments have been shown to be significantly effective in reducing cadmium (Cd) mobility, as well as pyrophyllite treatments in reducing lead (Pb) mobility in the studied soil, regardless of applied rates. The accumulation of heavy metals in leaves of maize grown on soil plots treated by zeolite and pyrophyllite, was found to be lower compared to the untreated plots. This finding was to be expected, considering the effects of these treatments on heavy metals mobility in the studied soil.

Dedifferentiation and acquisition of chromosomal instability in renal cell carcinoma portends dismal prognosis and aggressive clinical behavior. However, the absence of reliable experimental models dramatically impacts the understanding of mechanisms underlying malignant progression. Here we established an in vivo genetic platform to rapidly generate somatic mosaic genetically engineerd immune-competent mouse models of renal tumors, recapitulating the genomic and phenotypic features of these malignancies. Leveraging somatic chromosomal engineering, we demonstrated that ablation of the murine locus syntenic to human 9p21 drives the rapid expansion of aggressive mesenchymal clones with prominent metastatic behavior, characterized by early emergence of chromosomal instability, whole-genome duplication, and conserved patterns of aneuploidy. This model of punctuated equilibrium provides a remarkable example of cross-species convergent evolution. Significance To better understand the role of 9p21 in malignant progression, we generated a somatic mosaic GEMM of renal cancer, capturing the histological, genomic and evolutionary features of human disease. With this technology we demonstrated a critica role of 9p21 loss in metastatic evolution of RCC and provide a unique tool for testing new therapeutic treatments.

This paper presents a laboratory setup for testing and experimental verification of fault detection methods based on contactless measurement of power line magnetic field. The setup consists of a physical power line model scaled to laboratory conditions with two orthogonal measuring coils installed on one support pole underneath phase conductors. Voltages induced in the coils are amplified and filtered out by using analog electrical circuits and are fed to a digital data acquisition board. The sampled voltages are digitally processed by employing a generalized fault detection method previously developed by the authors. In this paper the main steps for designing the measuring coils, analog amplifying and filtering circuits are described in detail. The developed laboratory setup is verified by experiments for different shunt and series faults.

Optimal sizing of standalone hybrid renewable power supply for mobile telephony base stations is considered in this paper. This task is very complex due to stochastic nature of input variables such as wind speed, solar irradiance, ambient temperature and electric load. Further concern is modeling of the power consumed by cooling devices which is also uncertain variable dependent both on ambient conditions and power dissipation of telecommunication equipment. The realistic behavior of the station both in electrical and thermal terms can be analyzed only by a comprehensive probabilistic simulator. The basic idea of this paper is to systematically vary the main input parameters (rated powers of wind turbine and photovoltaic system along with battery capacity) and to run a Monte Carlo simulation for each considered variant observing the technical and economic indicators. Based on the minimum annual costs, it is possible to choose the best available investment solution. Simple optimization can be extended to multi-objective by adding some additional goals, such as minimizing the operating time of a diesel backup generator. The optimization method is tested on an illustrative example of a base station located in the Mediterranean area.

During a pandemic, mitigation as well as protection of system-critical or vulnerable institutions requires massive parallel, yet cost effective testing to monitor the spread of agents such as the current SARS-CoV2 virus. Here we present SARSeq, saliva analysis by RNA sequencing, as an approach to monitor presence of SARS-CoV2 and other respiratory viruses performed on tens of thousands of samples in parallel. SARSeq is based on next generation sequencing of multiple amplicons generated in parallel in a multiplexed RT-PCR reaction. It relies on a two-dimensional unique dual indexing strategy using four indices in total for unambiguous and scalable assignment of reads to individual samples. We calibrated this method using dilutions of synthetic RNA and virions to show sensitivity down to few molecules, and applied it to hundreds of patient samples validating robust performance across various sample types. Double blinded benchmarking to gold-standard quantitative RT-PCR performed in a clinical setting and a human diagnostics laboratory showed robust performance up to a Ct of 36. The false positive rate, likely due to cross contamination during sample pipetting, was estimated at 0.04-0.1%. In addition to SARS-CoV2, SARSeq detects Influenza A and B viruses as well as human rhinovirus and can be easily expanded to include detection of other pathogens. In sum, SARSeq is an ideal platform for differential diagnostic of respiratory diseases at a scale, as is required during a pandemic.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry. Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures. Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab. Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures. Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Background: Coronary artery disease as a consequence of atherosclerosis is the most common cause of morbidity and mortality in type 2 Diabetes Mellitus (DM) patients. Homocysteine (HCY), as one of the risk factors, and uric acid (UA) as the most common antioxidant in serum have their roles in the processes of inflammation and atherogenesis, which underlie the pathogenesis of acute myocardial infarction (AMI). The effect of HCY in cardiovascular disease is thought to be manifested primarily through oxidative damage, implying a potential correlation between the HCY level and antioxidant status. Since the data related to the diagnostic significance of both HCY and UA in diabetic patients with AMI are conflicting, and so far not reported in Bosnian patients, this research aimed to examine the association of HCY and UA levels with glomerular filtration rate (eGFR) and explore the pathophysiological significance of these data in Bosnian diabetic patients with AMI. Methods: This prospective research included 52 DM type 2 patients diagnosed with AMI. Blood samples were taken on admission and used for biochemical analysis. Results of the biochemical analyses were statistically analysed. Results: Elevated HCY and UA levels were observed in diabetic patients. Females have higher HCY compared to males. A positive correlation was revealed between HCY and UA and was confirmed with different HCY levels in subgroups with different UA level. A negative correlation was observed between UA and HbA1c, as well as between both HCY and UA with eGFR. Conclusions: These results contribute to the clarification of the biochemical mechanisms characteristic in AMI patients with DM. According to these results, we believe that joint measurement of HCY and UA could enable a better assessment of the prognosis for this group of patients. This kind of assessment, as well as regression analysis, can identify high-risk patients at an earlier stage when appropriate interventions can influence a better outcome in such patients.

Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high‐resolution computed tomography (HRCT) in juvenile SSc.