Metamizole Utilization and Expenditure During 6-Year Period: Serbia vs. Croatia

Background: Metamizole is a medication with analgesic, antipyretic, spasmolytic, and weak anti-inflammatory effects. The aim of our study was to evaluate a six-year trend in the utilization and expenditure of metamizole in comparison to other group of licensed non-opioid analgesics in Serbia and Croatia, in order to rationalize its use and prescribing in these countries.Methods: The data of metamizole vs. all other non-opioid analgesics utilization and expenditure in Serbia and Croatia was analyzed according to the WHO methodology and expressed as defined daily doses per 1,000 inhabitants per day (DDD/1,000 inhabitants/per day) and total costs, respectively, during the 6-year period from 2010 to 2015.Results: In the observed period, utilization of metamizole was 3.31 fold higher in Serbia than in Croatia (median in Serbia was 2.238 vs. 0.675 in Croatia DDD/1,000 inhabitants/per day/per year). Expenditure of metamizole in the same period was 5.29-fold higher in Serbia than in Croatia (median in Serbia was 1,738,192.51 €/per year vs. 328,355.03 €/per year in Croatia).Conclusion: Utilization and expenditure of non-opioid analgesics, including metamizole, in Serbia was significantly higher comparing with Croatia.Further research is needed to determine whether the current analgesic consumption in Serbia meets the needs of the patient. The benefits of metamizole should be weighed against the risk of metamizole-induced adverse effects. Until then, its prescribing should be based on indications and the appropriate duration of therapy

The discovery, distribution and diversity of DNA viruses associated with Drosophila melanogaster in Europe

International audienceDrosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here we report fourteen DNA viruses detected in a metagenomic analysis of approximately 6500 pool-sequenced Drosophila, sampled from 47 European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a dsRNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to 12 segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2% or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly-available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D. melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses

Drosophila evolution over space and time (DEST):A new population genomics resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in > 20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.DrosEU is funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). MK (M. Kapun) was supported by the Austrian Science Foundation (grant no. FWF P32275); JG by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); TF by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); MK (M. Kankare) by Academy of Finland grant 322980; VL by Danish Natural Science Research Council (FNU) grant 4002-00113B; FS Deutsche Forschungsgemeinschaft (DFG) grant STA1154/4-1, Project 408908608; JP by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; AU by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) grant 1737/17; MSV, MSR and MJ by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); AP, KE and MT by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551.Peer reviewe

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Corrigendum to: Drosophila Evolution over Space and Time (DEST): a New Population Genomics Resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in > 20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.DrosEU is funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). MK (M. Kapun) was supported by the Austrian Science Foundation (grant no. FWF P32275); JG by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); TF by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); MK (M. Kankare) by Academy of Finland grant 322980; VL by Danish Natural Science Research Council (FNU) grant 4002-00113B; FS Deutsche Forschungsgemeinschaft (DFG) grant STA1154/4-1, Project 408908608; JP by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; AU by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) grant 1737/17; MSV, MSR and MJ by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); AP, KE and MT by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551.Peer reviewe

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Deviations on the Swedish stock market : A study of three anomalies: The P/E-ratio, the January effect and the July effect

Aktiesparandet blir allt mer utbrett. I och med detta strävas det efter en så hög avkastning som möjligt, placerare vill helst slå index. Huvudantagandet inom finansiell ekonomi är att marknaden är effektiv, vilket speglas i den effektiva marknadshypotesen. Om marknader är effektiva bör det inte vara möjligt att generera överavkastning och anomalier som kan utnyttjas som investeringsstrategier borde inte förekomma.  Studiens syfte är att undersöka förekomsten av anomalier, mer precist: P/E-talseffekten, januarieffekten och julieffekten, under perioden 2000-2010.  Forskningsprocessen är av deduktiv karaktär, då redan befintliga teoriers riktighet testas med hjälp utav empiriska observationer. Vidare har vi vid studiens genomförande tillämpat ett kvantitativt tillvägagångssätt. Studien visar inte på några statistiskt signifikanta resultat då det gäller förekomsten av P/E-talseffekten. Med hjälp av regressionsanalys har vi sett att signifikant säsongvariation förekommer. Koefficienten för januari har högst värde som kan tyda på att under januari åstadkoms högst avkastning. Med andra ord har det gått att påvisa en januarieffekt hos små företag. Vi fick dock inga tecken på att julieffekten har existerat.Investments in stocks are becoming more widespread. High return is a priority and investors aim at earning higher return than share price index. The main assumption in finance is the one that assumes that the market is efficient. The theory that postulates market efficiency is the efficient market hypothesis. If markets indeed are efficient it should not be possible to beat the share price index and anomalies would not exist. The aim of this study is to investigate whether the Swedish stock market has shown signs of anomalies during the period of 2000-2010. The anomalies that will be examined are the January effect, the P/E ration and the July effect. The study is based on a deductive research process as it attempts to test already existing theories accuracy through empirical observations. The authors have used a quantitative approach testing and analyzing the underlying data in this study. The study did not find any statistically significant results regarding the existence of an anomaly related to the P/E ratio. The authors have been able to establish the existence of the January effect through a regression analysis. The January effect was present in small firms. There were no traces of a July effect

Deviations on the Swedish stock market : A study of three anomalies: The P/E-ratio, the January effect and the July effect

Aktiesparandet blir allt mer utbrett. I och med detta strävas det efter en så hög avkastning som möjligt, placerare vill helst slå index. Huvudantagandet inom finansiell ekonomi är att marknaden är effektiv, vilket speglas i den effektiva marknadshypotesen. Om marknader är effektiva bör det inte vara möjligt att generera överavkastning och anomalier som kan utnyttjas som investeringsstrategier borde inte förekomma.  Studiens syfte är att undersöka förekomsten av anomalier, mer precist: P/E-talseffekten, januarieffekten och julieffekten, under perioden 2000-2010.  Forskningsprocessen är av deduktiv karaktär, då redan befintliga teoriers riktighet testas med hjälp utav empiriska observationer. Vidare har vi vid studiens genomförande tillämpat ett kvantitativt tillvägagångssätt. Studien visar inte på några statistiskt signifikanta resultat då det gäller förekomsten av P/E-talseffekten. Med hjälp av regressionsanalys har vi sett att signifikant säsongvariation förekommer. Koefficienten för januari har högst värde som kan tyda på att under januari åstadkoms högst avkastning. Med andra ord har det gått att påvisa en januarieffekt hos små företag. Vi fick dock inga tecken på att julieffekten har existerat.Investments in stocks are becoming more widespread. High return is a priority and investors aim at earning higher return than share price index. The main assumption in finance is the one that assumes that the market is efficient. The theory that postulates market efficiency is the efficient market hypothesis. If markets indeed are efficient it should not be possible to beat the share price index and anomalies would not exist. The aim of this study is to investigate whether the Swedish stock market has shown signs of anomalies during the period of 2000-2010. The anomalies that will be examined are the January effect, the P/E ration and the July effect. The study is based on a deductive research process as it attempts to test already existing theories accuracy through empirical observations. The authors have used a quantitative approach testing and analyzing the underlying data in this study. The study did not find any statistically significant results regarding the existence of an anomaly related to the P/E ratio. The authors have been able to establish the existence of the January effect through a regression analysis. The January effect was present in small firms. There were no traces of a July effect