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Supplemental Digital Content is available in the text.Given the approval of dabrafenib in patients with BRAF-mutant metastatic melanoma, a better understanding of treatment patterns and clinical outcomes with dabrafenib in a clinical setting is warranted. We performed a retrospective chart review of patients who received dabrafenib in a compassionate use setting through the Named Patient Program (DESCRIBE I study) during December 2010–August 2013 in Europe, New Zealand and Australia. Of the 331 Named Patient Program patients included, the majority (95.8%) had stage IV disease at dabrafenib initiation and 39.9% had brain metastases (BMs). Dabrafenib was used first line in 67.7% of patients, and median treatment duration was 6.4 months. Dabrafenib was well tolerated. Common grade 2/3 adverse events were hyperkeratosis (7.6%), pyrexia/fever (6.6%), fatigue (5.1%), hand-foot syndrome (5.4%) and nausea (3.6%). Overall response rate was 45.9%, median progression-free survival was 5.2 months (95% confidence interval, 4.2–6.1 months), and median overall survival was 12.4 months (95% confidence interval, 10.2–15.0 months). In patients with known brain metastases (n= 132) versus patients without (n= 199), overall response rate was 42.4% versus 48.2%, progression-free survival was 3.9 months (95% confidence interval, 3.8–5.5 months) versus 5.9 months (95% confidence interval, 4.8–7.8 months) and overall survival was 9.5 months (95% confidence interval, 6.7–12.4 months) versus 15 months (95% confidence interval, 11.1–20.5 months), respectively. Safety and effectiveness of dabrafenib in patients with unresectable advanced BRAFV600–mutant melanoma treated in an Named Patient Program was similar to the clinical trial experience, demonstrating effectiveness of dabrafenib in a nontrial setting.

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today1. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations2–5. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere6,7, which—given methane’s lifetime of several centuries—predicts an even, well mixed distribution of methane1,6,8. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections2,4. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater4would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally.

ABSTRACTSince the second part of the twentieth century, Chile has become the largest copper producer in the world, being the pyrometallurgical processing of sulfides concentrates a central part of it.Since the introduction of the Peirce-Smith and later the Hoboken converters in Chilean smelters, some modifications were made to these reactors, including feeding of copper concentrate and intensive oxygen enrichment utilisation to increase their productivity. These modifications, and the use of bone dry concentrates, later became part of the new Teniente technology to smelt concentrates. All these innovations also influenced other processes, such as slag and gas treatment.This paper shows how pyrometallurgical processing of copper concentrates has been developed in Chile and how the Teniente reactor was conceived and implemented. Also, a comparison between nonferrous and ferrous technologies in terms of instrumentation and control, and some new processes being developed at laboratory and scale are shown.

Patients with cancer are presumed to have a higher risk to contract SARS-CoV-2 infection, because of their immunosuppressed status. The impact and course of COVID-19 infection in cancer patients receiving immunotherapy remains unknown.

Geoffroy’s cat (Leopardus geoffroyi) is a small Neotropical felid whose social behavior remains poorly understood. We used simultaneous radiotelemetry (4 males and 3 females) and camera trapping to examine the spatial structure and dynamics of a population of this species in the Brazilian pampas (part of the Uruguayan Savannah ecoregion), including assessment of interindividual genetic relatedness. Home ranges (HRs) and core areas of males were larger than those of females. Males were significantly heavier than females, and linear regression analyses indicated that body mass of males significantly influenced HR size, whereas the relationship was not significant for females. When we performed a joint analysis comparing our data to those reported previously for other study sites, we observed the same patterns. We detected extensive HR and core area overlap among most of our monitored individuals, with no clear sex-based pattern. Moreover, our molecular data indicated that most of the sampled individuals were unrelated, and that the levels of HR and core area overlap were not significantly influenced by genetic relatedness. These results suggest that some interindividual tolerance and relaxation in territoriality may occur in Geoffroy’s cat. We detected only minor changes in HR and core area size and overlap between seasons, indicating that the spatial structure we observed was temporally stable. On a broader perspective, our cross-site comparisons illustrate the usefulness of performing multiple ecological studies employing comparable methods at different locations to better understand the ecology of wild felid populations.A espécie Leopardus geoffroyié um felídeo neotropical de pequeno porte, cujo comportamento social é ainda pouco conhecido. O presente estudo examinou a estrutura e a dinâmica espacial de uma população dessa espécie, incluindo a primeira avaliação da relação de parentesco entre seus indivíduos. Além disso, os tamanhos de áreas de vida e a massa corporal da população estudada foram comparados estatisticamente com os resultados de estudos prévios, gerando dados globais para a espécie. O trabalho de campo foi conduzido entre novembro de 2013 e setembro de 2015, em propriedades rurais localizadas na Serra do Caverá, sul do Brasil (na ecorregião da Savana Uruguai). Foram registradas 516 imagens de L. geoffroyie foram capturados 12 indivíduos desta espécie, sete (4M e 3F) dos quais puderam ser monitorados com rádio-telemetria. Observou-se que os machos possuem áreas de vida, de uso e massa corporal maiores do que as fêmeas. Os resultados das análises de regressão linear indicaram que a massa corporal dos machos influenciou positiva e significativamente o tamanho das áreas de vida dos mesmos, relação esta que não ocorreu entre as fêmeas. Esse resultado ocorreu tanto na população estudada como nos dados globais. Também foi observada uma extensa sobreposição de áreas de vida e de uso, indicando algum grau de socialidade (tolerância) nesta população. Os resultados da análise de parentesco indicaram que a maioria dos indivíduos capturados desta população não eram parentes. Além disso, a relação genética parece não influenciar a sobreposição de área de vida, o que sugere que esta população, na escala estudada, possui uma estrutura sócio-espacial distinta da proposição tradicional na qual os machos tenderiam a dispersar por maiores distâncias e as fêmeas seriam filopátricas. Em uma perspectiva mais ampla, as comparações aqui apresentadas ilustram a utilidade de se realizar estudos ecológicos empregando métodos comparáveis ​​em diferentes locais, a fim de entender melhor a ecologia das populações de felídeos silvestres.

The Neotropical region currently harbors 8 recognized species of small cats, including the margay (Leopardus wiedii) and jaguarundi (Puma yagouaroundi). These similar-sized species have broad geographic distributions and commonly occur in sympatry. We constructed species occurrence databases and used the maximum entropy (Maxent) modeling approach to develop models of habitat suitability for each of these species. We identified the environmental predictors with the highest importance for species occurrence and evaluated how they influence habitat suitability for both wild cats. Variables related to temperature and precipitation were good predictors of species occurrence, with both cats responding similarly to them. However, margay showed higher variation in habitat suitability depending on local climatic predictors. The estimated models indicated high niche similarity (> 76%) between these cats, but despite this we identified different areas with the most favorable conditions for each species’ occurrence. Approximately 50% and 72% of the entire suitable area were estimated as being moderately to highly suitable for margay and jaguarundi, respectively, with the margay model comprising a higher proportion of forest environments in comparison to that of the jaguarundi. These findings will be relevant in the context of conservation planning when indicating the priority areas for their long-term preservation.A região Neotropical possui atualmente oito espécies de pequenos felídeos, incluindo o gato-maracajá (Leopardus wiedii) e o jaguarundi (Puma yagouaroundi). Estas duas espécies apresentam ampla distribuição geográfica nos neotrópicos, ocorrendo geralmente em simpatria e compartilhando vários aspectos biogeográficos. Neste trabalho, construímos um banco com dados de ocorrência destas espécies e usamos o método de máxima entropia (Maxent) para obter modelos de adequabilidade de habitat para cada uma delas. Os preditores ambientais com maior percentual de contribuição aos modelos gerados foram identificados, sendo ainda avaliado como cada um deles influencia na adequabilidade de habitat estimada para as espécies. Variáveis associadas com temperatura e precipitação foram identificadas como importantes para a ocorrência das espécies, com os dois felídeos respondendo similarmente a elas. No entanto, para o gato-maracajá foi identificada uma maior variação na adequabilidade de habitat estimada, de acordo com os valores locais das variáveis climáticas. Os modelos resultaram em uma grande similaridade nos nichos ecológicos (> 76%), mas apesar disto diferentes áreas foram identificadas como apresentando as condições mais favoráveis à ocorrência de cada espécie. Considerando a área total estimada como adequada para cada um dos felídeos, apenas 50% e 72% destas foram classificadas como moderada a altamente adequadas para a ocorrência do gato-maracajá e do jaguarundi, respectivamente, com o modelo gerado para o gato-maracajá compreendendo uma maior proporção de ambientes florestais em comparação ao modelo gerado para o jaguarundi. Estes resultados provêm informações relevantes para a compreensão da ecologia destas espécies, bem como para o delineamento de estratégias de conservação com foco nestes felídeos, como a indicação de áreas prioritárias à sua preservação em longo prazo.