Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)

Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N = 556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p < .0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p = .36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR = 0.56; p = .015), and worse survival on chronoFLO4 (HR = 1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy.info:eu-repo/semantics/publishedVersio

Does community deprivation determine longevity after the age of 75? A cross-national analysis

Objectives: Analyze the association between socioeconomic deprivation and old-age survival in Europe, and investigate whether it varies by country and gender. Methods: Our study incorporated five countries (Portugal, Spain, France, Italy, and England). A 10-year survival rate expressing the proportion of population aged 75–84 years who reached 85–94 years old was calculated at area-level for 2001–11. To estimate associations, we used Bayesian spatial models and a transnational measure of deprivation. Attributable/prevention fractions were calculated. Results: Overall, there was a significant association between deprivation and survival in both genders. In England that association was stronger, following a dose–response relation. Although lesser in magnitude, significant associations were observed in Spain and Italy, whereas in France and Portugal these were even weaker. The elimination of socioeconomic differences between areas would increase survival by 7.1%, and even a small reduction in socioeconomic differences would lead to a 1.6% increase. Conclusions: Socioeconomic deprivation was associated with survival among older adults at ecological-level, although with varying magnitude across countries. Reasons for such cross-country differences should be sought. Our results emphasize the importance of reducing socioeconomic differences between areas.This work was supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of project UID/BIM/04293/2013. AIR and MFP would also like to thank to FC—Fundação para a Ciência e a Tecnologia for the Grants PTDC/SAU-EPI/113424/2009 and SFRH/BD/82529/2011. MSC was supported by CNpQ (309692/2013-0) and FAPERJ (E-26/203.557/2014).We are very grateful to the National Statistic Offices for sending us the required data and to all the members of the European Deprivation Index (EDI) team. The authors would like to thank Rogério Ribeiro for the help in preparing visual supports, Alexandra Guttentag for her work as language editor, and the anonymous reviewers for their highly valuable corrections and suggestions

Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy

Cancer is the second leading cause of death in the world. Given that cancer is a highly individualized disease, predicting the best chemotherapeutic treatment for individual patients can be difficult. Ex vivo models such as mouse patient-derived xenografts (PDX) and organoids are being developed to predict patient-specific chemosensitivity profiles before treatment in the clinic. Although promising, these models have significant disadvantages including long growth times that introduce genetic and epigenetic changes to the tumor. The zebrafish xenograft assay is ideal for personalized medicine. Imaging of the small, transparent fry is unparalleled among vertebrate organisms. In addition, the speed (5-7 days) and small patient tissue requirements (100-200 cells per animal) are unique features of the zebrafish xenograft model that enable patient-specific chemosensitivity analyses.info:eu-repo/semantics/publishedVersio

DrosoPhyla: genomic resources for drosophilid phylogeny and systematics

The vinegar fly Drosophila melanogaster is a pivotal model for invertebrate development, genetics, physiology, neuroscience, and disease. The whole family Drosophilidae, which contains over 4000 species, offers a plethora of cases for comparative and evolutionary studies. Despite a long history of phylogenetic inference, many relationships remain unresolved among the groups and genera in the Drosophilidae. To clarify these relationships, we first developed a set of new genomic markers and assembled a multilocus data set of 17 genes from 704 species of Drosophilidae. We then inferred well-supported group and species trees for this family. Additionally, we were able to determine the phylogenetic position of some previously unplaced species. These results establish a new framework for investigating the evolution of traits in fruit flies, as well as valuable resources for systematics

O sistema brasileiro de instituições financeiras subnacionais para o desenvolvimento : um panorama

É permitida a reprodução deste texto e dos dados nele contidos, desde que citada a fonte. Reproduções para fins comerciais são proibidas.Bibliografia: p. 40-42.O objetivo deste trabalho é oferecer um panorama geral sobre a experiência brasileira recente com o sistema composto por instituições financeiras públicas, que chamaremos de subnacionais, voltadas para o financiamento do desenvolvimento: um banco regional de desenvolvimento, três bancos estaduais de desenvolvimento e 13 agências estaduais de fomento. Pretende-se mostrar que, em geral, este sistema é débil, possuindo fontes de funding pouco diversificadas, dependente do Banco Nacional de Desenvolvimento Econômico e Social (BNDES) e dos governos estaduais. Assim, as possibilidades de expansão dessas instituições dependem fortemente da dinâmica das respectivas economias estaduais e de suas capacidades arrecadatórias ou de fatores exógenos, tais como o acesso aos recursos do BNDES e dos fundos constitucionais – os quais, por sua vez, dependem da estratégia de atuação do BNDES e dos bancos federais gestores dos fundos constitucionais e dos critérios de escolha dos intermediários financeiros por parte dessas instituições federais. Por outro lado, as operações de crédito oriundas das instituições financeiras públicas subnacionais para financiamento do desenvolvimento (IFDs-SN) parecem ser qualitativamente distintas dos bancos públicos federais brasileiros, por exemplo, ao privilegiar os setores de pessoas físicas – aqui entendidas, como se verá mais adiante, como microempreendores. Os movimentos observados dessas operações indicam também que essas instituições não foram capazes de acompanhar a contento o recente ciclo expansivo de crédito pelo qual passou a economia brasileira desde 2004. De fato, excetuando-se o setor comercial, em todos os demais as operações de crédito cresceram a taxas inferiores à média do Sistema Financeiro Nacional (SFN) ou mesmo dos bancos públicos. Em 2009 constitui uma exceção, revelando que as IFDs-SN também contribuíram para a ação anticíclica implementada pelos bancos públicos brasileiros por ocasião da crise financeira de 2008-2009