49 research outputs found

    Pervasive gaps in Amazonian ecological research

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    Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

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    PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

    Pervasive gaps in Amazonian ecological research

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    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

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

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    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

    Pervasive gaps in Amazonian ecological research

    Get PDF
    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding 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,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 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 underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities 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 organism 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 neglected 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 lost

    Função respiratória em filhos de mães asmáticas Respiratory function in children of asthmatic mothers

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    OBJETIVO: Avaliar a função pulmonar e as manifestações clínicas sugestivas de asma em filhos de mães com diagnóstico médico referido de asma. MÉTODOS: Estudo observacional transversal analítico aninhado a uma coorte de 4.757 parturientes. Foram avaliadas 86 crianças aos seis anos de idade, filhas de mães com diagnóstico médico de asma antes da gestação. Foram coletadas informações referentes a sintomatologias clínicas de atopias e doenças respiratórias, variáveis socioeconômicas e de exposição; tendo sido as crianças submetidas à espirometria. RESULTADOS: Foram encontrados 30,3% de alterações espirométricas, havendo predomínio do diagnóstico de asma nos que apresentaram padrão obstrutivo. Diagnóstico médico pregresso de asma ocorreu em 9,3% das crianças; contudo, o diagnóstico estabelecido a partir da presença e frequência dos sintomas de asma representou 18,6%. Das 86 crianças participantes, 37,2% tiveram um escore de cinco ou mais pontos no questionário ISAAC, estando isso associado à alteração do padrão espirométrico (p = 0,002). Após a regressão logística múltipla, maior escolaridade paterna, maior número de quartos no domicílio e o fato de a mãe não ter apresentado "chiado" durante a gestação foram estatisticamente significantes como fatores protetores para a presença de distúrbio ventilatório à espirometria. CONCLUSÕES: A frequência de alterações do teste espirométrico em filhos de mães asmáticas foi alta, com o padrão restritivo ocorrendo mais vezes que o obstrutivo. Houve uma maior ocorrência de exames obstrutivos naqueles que apresentavam sintomatologia clínica de asma, com uma frequência de diagnóstico clínico de asma superior à encontrada na literatura.OBJECTIVE: To evaluate lung function and clinical manifestations suggestive of asthma in children of mothers with a reported medical diagnosis of asthma. METHODS: An observational cross-sectional analytical study nested in a cohort of 4,757 pregnant women. A total of 86 six-year-old children were evaluated, born to mothers with a medical diagnosis of asthma before pregnancy. Information was collected regarding clinical symptoms of atopy and respiratory diseases, as well as socioeconomic and exposure variables; the children were submitted to spirometry. RESULTS: Spirometric alterations were observed in 30.3% of cases, with a prevalence of asthma in those who had an obstructive pattern. 9.3% of the children had a previous medical diagnosis of asthma; however, the established diagnosis based on the presence and frequency of asthma symptoms was 18.6%. Of the 86 participating children, 37.2% had a score of five or more points in the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which was associated with spirometry alterations (p = 0.002). After multiple logistic regression analysis, higher paternal education, higher number of bedrooms in the family's home, and mother who did not have "wheezing" episodes during pregnancy were statistically significant as protective factors for the presence of respiratory disorder detected by spirometry. CONCLUSIONS: The frequency of spirometry alterations in children of asthmatic mothers was high; the restrictive pattern was more often observed that the obstructive. There was a higher incidence of obstructive test results in those who presented clinical symptoms of asthma, with a higher frequency of clinical diagnosis of asthma than that found in the literature

    Respiratory function in children of asthmatic mothers

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    AbstractObjectiveTo evaluate lung function and clinical manifestations suggestive of asthma in children of mothers with a reported medical diagnosis of asthma.MethodsAn observational cross-sectional analytical study nested in a cohort of 4,757 pregnant women. A total of 86 six-year-old children were evaluated, born to mothers with a medical diagnosis of asthma before pregnancy. Information was collected regarding clinical symptoms of atopy and respiratory diseases, as well as socioeconomic and exposure variables; the children were submitted to spirometry.ResultsSpirometric alterations were observed in 30.3% of cases, with a prevalence of asthma in those who had an obstructive pattern. 9.3% of the children had a previous medical diagnosis of asthma; however, the established diagnosis based on the presence and frequency of asthma symptoms was 18.6%. Of the 86 participating children, 37.2% had a score of five or more points in the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which was associated with spirometry alterations (p=0.002). After multiple logistic regression analysis, higher paternal education, higher number of bedrooms in the family's home, and mother who did not have “wheezing” episodes during pregnancy were statistically significant as protective factors for the presence of respiratory disorder detected by spirometry.ConclusionsThe frequency of spirometry alterations in children of asthmatic mothers was high; the restrictive pattern was more often observed that the obstructive. There was a higher incidence of obstructive test results in those who presented clinical symptoms of asthma, with a higher frequency of clinical diagnosis of asthma than that found in the literature
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