Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Use of a mathematical model to estimate the impact of shrimp pen culture at Patos Lagoon estuary, Brazil

Ecological modeling has been used as a tool to estimate potential impacts caused by aquaculture to the surrounding environment. In this work, a mathematical model was applied to estimate the maximum amount of pink shrimp (Farfantepenaeus paulensis) culture units (3,100m2 pen enclosures) that could be installed at two shallow estuarine bays of Patos Lagoon (known as Coreia and Porto do Rei) with no significant effects on either water quality or viability of the culture system. To calibrate the model, information about the culture of Litopenaeus vannamei and F. paulensis as well as field data (influence of netting material, water current speed and nitrogen concentrations) were used. Under a bad scenario (water current velocity of 0.01m s–1 and a mesh clogging effect of 40%), it would be possible to install up to 29 pens at the Coreia bay, and 39 pens at the Porto do Rei bay. Results indicate that the model was useful in determining the maximum number of culture units that could be installed at these bays, and thus have the potential to become an important tool in the definition of environmental management strategies in relation to aquaculture development.Modelos ecológicos têm sido utilizados como ferramenta para avaliar potenciais impactos ambientais causados pela aquicultura. Neste trabalho, foi aplicado um modelo matemático para estimar a quantidade máxima de unidades de produção (cercados com 3.100 m2) do camarão-rosa Farfantepenaeus paulensis que podem ser instalados em duas baías rasas no estuário da Lagoa dos Patos (conhecidas como Coreia e Porto do Rei), sem efeitos significativos sobre a qualidade da água e viabilidade do sistema de engorda. Para calibrar o modelo, informações sobre a criação de Litopenaeus vannamei e F. paulensis, bem como dados de campo (influência de material de pano, a velocidade da corrente da água e concentração de nitrogênio) foram utilizados. Considerando um cenário ruim, velocidade da corrente da água de 0,01 m s–1 e um efeito de colmatação da malha de 40%, seria possível instalar no máximo 29 cercados na baía Coreia e 39 na baia Porto do Rei. Os resultados indicam que o modelo foi útil para determinar o número máximo de unidades de produção que podem ser instalados nestes compartimentos e, portanto, tem o potencial para se tornar uma ferramenta importante na definição de estratégias de gestão ambiental, em relação ao desenvolvimento da aquicultura

Short- and long-term chlorophyll a variability in the shallow microtidal Patos Lagoon estuary, southern Brazil

In the shallow microtidal Patos Lagoon estuary, southern Brazil (32° 07′ S–52° 06′ W), chlorophyll a (Chl a) variability was studied at different time scales during the last 25 years (hourly–daily sampling in 1984/1985; weekly sampling in 1986 and from 1988 to 1990; monthly sampling from 1993 to 2008). Phytoplankton biomass variation seems to be most influenced by hydrology, which is primarily driven by meteorological factors like wind, rainfall, and evaporation. However, it was observed that the hydrological driving forces play different roles at different time scales. For instance, short-term Chl a variability is mainly controlled by winds, while long-term changes are related to the freshwater input by rainfall. Significant correlation was found between the total amount of rain in the year and the mean annual value of Chl a, though this relationship was linear until 1,500 mm of rain per year. After this threshold, mean annual Chl a values dropped significantly, probably due to a washout of the produced biomass from the estuary. Similarly, low rainfall levels and drought years lead to small phytoplankton biomass due to scarcity of nutrient, mainly silicate, or a possible inhibitory effect generated by high ammonium concentration. In this sense, large-scale Chl a variability would be related to the El Niño-Southern Oscillation climatic anomaly, which influences the rainfall levels in Southern Brazil, though sampling periodicity has also great influence on this relationship. No Chl a or nutrient enrichment was observed in the estuarine region along the last years, indicating that this estuary is not subject to an eutrophication process. In contrast, signals of an ongoing oligotrophication are observed, possibly a remote effect of the eutrophication in the Northern area of the lagoon where the phytoplankton nutrients uptake may act as a biological filter mechanism