Analysis of reporting to the Portuguese Pharmacovigilance System

Background Biological drugs have been successfully tested in asthma, being especially effective in the most severe forms of the disease. In parallel, safety issues have also emerged and have been recognized as a crucial aspect that needs to be monitored. The purpose of this study was to characterise the safety profile of biologicals used in asthma, by carrying out an analysis of Portuguese spontaneous reports (SR) of suspected adverse reactions to these drugs (ADR). Methods Retrospective analysis of SR of suspected ADR attributed to omalizumab and mepolizumab, sent to the National Pharmacovigilance System (SNF), since market launch until October 2018. We evaluated patients´ demographic data, as well as characteristics and seriousness of reactions. Results For omalizumab, from February 2006 to October 2018, there was an average annual reporting rate of 0.1978 reported cases per thousand severe asthmatics, with an increasing trend as years progressed. In the two years that mepolizumab has been subject to reports there was an average annual reporting rate of 0.1257 reported cases per thousand severe asthmatics. After all duplicate reports were removed, there was a total of 127 SR including 391 suspected ADR for omalizumab, and 10 SRs including 20 suspected ADRs for mepolizumab. For both omalizumab and mepolizumab the vast majority of patients were female (75.6% and 90.0%, respectively), and between 18 and 64 years old (61.4% and 50.0%, respectively). With omalizumab, the most frequent suspected ADRs were “respiratory, thoracic and mediastinal disorders”, “investigations” and “general disorders and administration site conditions”, according to System Organ Class (SOC), and “asthma”, “arthralgia” and “drug ineffective”, according to Preferred Term (PT). With mepolizumab, the most frequent suspected ADR were the “musculoskeletal and connective tissue disorders” and “general disorders and administration site conditions” SOCs, and the “arthralgia” PT. Regarding seriousness, 71.7% of the reports for omalizumab were serious, with a single fatal episode, 2 cases of anaphylaxis, 12 cases of malignant neoplasms and 2 abortions. Only 20.0% of the reports for mepolizumab were considered serious. Conclusions Despite limitations to this kind of study, our conclusions are in line with other studies, which show the favourable benefit-risk profile of this recent therapeutic approach. Our study also suggests that it is necessary to continue to develop educational programmes in order to get a better reporting system.Introdução Medicamentos biológicos foram testados com sucesso na asma, sendo especialmente eficazes nas formas mais graves da doença. Paralelamente, emergiu também a questão da segurança, tendo sido reconhecida como um aspecto crucial que necessita ser monitorizado. Estima-se que a grande maioria das reações adversas medicamentosas (RAM) graves seja apenas detectada na fase pós-comercialização, sendo fundamental a implementação de farmacovigilância contínua dos medicamentos e os sistemas de notificação espontãnea são um dos pilares dessa vigilância. O objetivo deste estudo foi caracterizar o perfil de segurança dos biológicos utilizados na asma, através de uma análise das notificações espontâneas (NE) de suspeitas de RAM notificadas em Portugal. Métodos Análise retrospectiva das NE de suspeitas de RAM atribuídas ao omalizumab e ao mepolizumab, enviadas ao Sistema Nacional de Farmacovigilância (SNF), desde o início da sua comercialização até outubro de 2018. Foi avaliada a evolução anual da frequência das NE, bem como foi realizada uma caracterização demográfica dos casos, considerando sexo e faixa etária. Cada notificação foi classificada de acordo com a sua gravidade e, nos casos graves, foi especificado qual o critério de gravidade em questão. As suspeitas de RAM foram avaliadas e categorizadas de acordo com o Preferred Term (PT) e System Organ Class (SOC) do dicionário MedDRA (Medical Dictionary for Regulatory Activities). Também foi verificado se as suspeitas de RAM do estudo estavam ou não descritas no Resumo das Características do Medicamento (RCM) do respectivo fármaco. Por último, foi realizada uma análise mais aprofundada dos casos graves com termos da terminologia MedDRA pertencentes à lista de Important Medical Event (IME). Resultados No caso do omalizumab, desde fevereiro de 2006 a outubro de 2018, houve uma taxa de notificação média anual de 0.1978 casos/1000 asmáticos graves, com uma tendência de notificação crescente à medida que os anos progrediram e com quase metade de todos os casos (48.5%) a serem registrados em 2017 e 2018. Nos dois anos em que o mepolizumab foi alvo de notificações, registou-se uma taxa de notificação média anual de 0.1257 casos/1000 asmáticos graves. Após exclusão dos duplicados, houve um total de 127 NE, incluindo 391 suspeitas de RAM para o omalizumab, e 10 NE, incluindo 20 suspeitas de RAMs para o mepolizumab. Quanto à caracterização demográfica, nos casos do omalizumab e do mepolizumab, a grande maioria dos pacientes era do sexo feminino (75.6% e 90.0%, respectivamente) e de idade compreendida entre 18 e 64 anos (61.4% e 50.0%, respectivamente). Com o omalizumab, as suspeitas de RAM mais frequentes foram “doenças respiratórias, torácicas e do mediastino”, “exames complementares de diagnóstico” e “perturbações gerais e alterações no local de administração”, de acordo com o SOC, e “asma”, “artralgia” e “ausência de resposta terapêutica”, segundo o PT. Houve 8 casos de reacções no local da injecção. No caso do mepolizumab, as suspeitas de RAM mais frequentes foram os SOCs “Afecções musculosqueléticas e dos tecidos conjuntivos” e “perturbações gerais e alterações no local de administração”, e o PT “artralgia”. Após analisar quanto à presença das suspeitas de RAM nos RCMs, 53.4% não estavam descritas com o omalizumab e 41.2% não estavam descritas com o mepolizumab. Em relação à gravidade, 71.7% das notificações do omalizumab foram graves, com um único episódio fatal (um acidente de viação), dois casos de anafilaxia, 12 casos de neoplasias malignas (com 6 casos de tumores malignos da mama) e dois abortos. Apenas 20.0% das notificações do mepolizumab foram consideradas graves. Conclusões Apesar das limitações associadas a este tipo de estudo, as nossas conclusões estão de acordo com outros estudos que demostram um perfil favorável de risco-benefício desta terapêutica recente. O nosso estudo sugere também que é necessário continuar a desenvolver programas educacionais para obter um sistema de notificação mais eficaz, informando as pessoas acerca da importância de terem um papel ativo na monitorização da segurança dos fármacos através da notificação de suspeitas de RAM às autoridades, e fazendo uma descrição o mais completa possível dos casos

Mitigation of urban heat island effects by thermochromic asphalt pavement

Asphalt road pavements are usually dark and, consequently, have a low albedo. Therefore, they absorb energy as heat, increasing the Urban Heat Island (UHI) effect, which impacts the environment, energy consumption, and human health. Through the functionalization with thermochromic materials (TM), this work aims to develop a smart asphalt pavement able to change its surface color, increasing the reflectance, and thus mitigate this phenomenon. To achieve this goal, asphalt substrates were functionalized by a surface spray coating of a thermochromic solution (TS) containing aqueous solution of thermochromic microcapsules (thermocapsules), dye, and epoxy resin. To evaluate the functionalization features, Fourier Transform Infrared Spectroscopy (FTIR), and Thermal Differential test (TDT) with cyclic temperature variation were performed in the functionalized asphalt binder. Moreover, Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectrometry (EDS), a Quick Ultraviolet Accelerated Weathering Test (QUV) with Colorimetry test, and an adaptation of the Accelerated Polishing Test (APT) were performed on the functionalized asphalt mixture. The results indicate that the functionalization of asphalt substrates with TS exhibits a reversible color-change ability, higher luminosity values when subjected to temperatures above 30 C, and wear resistance

Building a Portuguese Coalition for Biodiversity Genomics

The diverse physiography of the Portuguese land and marine territory, spanning from continental Europe to the Atlantic archipelagos, has made it an important repository of biodiversity throughout the Pleistocene glacial cycles, leading to a remarkable diversity of species and ecosystems. This rich biodiversity is under threat from anthropogenic drivers, such as climate change, invasive species, land use changes, overexploitation or pathogen (re)emergence. The inventory, characterization and study of biodiversity at inter- and intra-specific levels using genomics is crucial to promote its preservation and recovery by informing biodiversity conservation policies, management measures and research. The participation of researchers from Portuguese institutions in the European Reference Genome Atlas (ERGA) initiative, and its pilot effort to generate reference genomes for European biodiversity, has reinforced the establishment of Biogenome Portugal. This nascent institutional network will connect the national community of researchers in genomics. Here, we describe the Portuguese contribution to ERGA’s pilot effort, which will generate high-quality reference genomes of six species from Portugal that are endemic, iconic and/or endangered, and include plants, insects and vertebrates (fish, birds and mammals) from mainland Portugal or the Azores islands. In addition, we outline the objectives of Biogenome Portugal, which aims to (i) promote scientific collaboration, (ii) contribute to advanced training, (iii) stimulate the participation of institutions and researchers based in Portugal in international biodiversity genomics initiatives, and (iv) contribute to the transfer of knowledge to stakeholders and engaging the public to preserve biodiversity. This initiative will strengthen biodiversity genomics research in Portugal and fuel the genomic inventory of Portuguese eukaryotic species. Such efforts will be critical to the conservation of the country’s rich biodiversity and will contribute to ERGA’s goal of generating reference genomes for European species.info:eu-repo/semantics/publishedVersio

Local hydrological conditions influence tree diversity and composition across the Amazon basin

Tree diversity and composition in Amazonia are known to be strongly determined by the water supplied by precipitation. Nevertheless, within the same climatic regime, water availability is modulated by local topography and soil characteristics (hereafter referred to as local hydrological conditions), varying from saturated and poorly drained to well-drained and potentially dry areas. While these conditions may be expected to influence species distribution, the impacts of local hydrological conditions on tree diversity and composition remain poorly understood at the whole Amazon basin scale. Using a dataset of 443 1-ha non-flooded forest plots distributed across the basin, we investigate how local hydrological conditions influence 1) tree alpha diversity, 2) the community-weighted wood density mean (CWM-wd) – a proxy for hydraulic resistance and 3) tree species composition. We find that the effect of local hydrological conditions on tree diversity depends on climate, being more evident in wetter forests, where diversity increases towards locations with well-drained soils. CWM-wd increased towards better drained soils in Southern and Western Amazonia. Tree species composition changed along local soil hydrological gradients in Central-Eastern, Western and Southern Amazonia, and those changes were correlated with changes in the mean wood density of plots. Our results suggest that local hydrological gradients filter species, influencing the diversity and composition of Amazonian forests. Overall, this study shows that the effect of local hydrological conditions is pervasive, extending over wide Amazonian regions, and reinforces the importance of accounting for local topography and hydrology to better understand the likely response and resilience of forests to increased frequency of extreme climate events and rising temperatures

Mapping density, diversity and species-richness of the Amazon tree flora

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Aim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran\u27s eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R$^{2}$ = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R$^{2}$ = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

AimAmazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.LocationAmazonia.TaxonAngiosperms (Magnoliids; Monocots; Eudicots).MethodsData for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.ResultsIn the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.Main ConclusionNumerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio