35 research outputs found
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Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.
BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health
Terrorists, rioters and crocodiles: The political symbolism of an Olympic monster
This is a post-peer-review, pre-copyedit version of an article published in British Politics. The definitive publisher-authenticated version - British Politics, 2014, 9(2), pp. 161-181 - is available online at: http://www.palgrave-journals.com/bp/journal/v9/n2/full/bp201317a.htmlIn August 2005, just a month after the announcement that London had succeeded in its bid to host the 2012 Olympic Games, the UK national press witnessed a brief rash of stories alleging the presence of a crocodile or similar water monster lurking beneath the surface of the River Lea – the river that runs from the town of Luton in Bedfordshire down to join the Thames adjacent to the Olympic site. This story re-emerged in November 2011 when a campaigner against the environmental impact of the Olympics on the river area claimed to have seen further evidence of crocodilian activity. This paper will explore the reasons for the proliferation of this story, in terms both of its function as a metonymic news-hook (it opened up directly related concerns as to the impact, organization and security of the Games) and of its metaphorical significance (its incarnation of a superstructure’s fears of an emerging threat of a monstrous underclass – one which might at once comprise terrorists, rioters and anti-establishment campaigners). It will conclude by suggesting that this monstrous myth might hold within it the possibility of the convergence of populist news media and popular democracy
Multi-decadal changes in tundra environments and ecosystems: Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF).
Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in sub-arctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies
A critical review and development of a conceptual model of exclusion from social relations for older people
Social exclusion is complex and dynamic, and it leads to the non-realization of social, economic, political or cultural rights or participation within a society. This critical review takes stock of the literature on exclusion of social relations. Social relations are defined as comprising social resources, social connections and social networks. An evidence review group undertook a critical review which integrates, interprets and synthesizes information across studies to develop a conceptual model of exclusion from social relations. The resulting model is a subjective interpretation of the literature and is intended to be the starting point for further evaluations. The conceptual model identifies individual risks for exclusion from social relations (personal attributes, biological and neurological risk, retirement, socio-economic status, exclusion from material resources and migration). It incorporates the evaluation of social relations, and the influence of psychosocial resources and socioemotional processes, sociocultural, social-structural, environmental and policy contextual influences on exclusion from social relations. It includes distal outcomes of exclusion from social relations, that is, individual well-being, health and functioning, social opportunities and social cohesion. The dynamic relationships between elements of the model are also reported. We conclude that the model provides a subjective interpretation of the data and an excellent starting point for further phases of conceptual development and systematic evaluation(s). Future research needs to consider the use of sophisticated analytical tools and an interdisciplinary approach in order to understand the underlying biological and ecopsychosocial associations that contribute to individual and dynamic differences in the experience of exclusion from social relation
Long-Term Vegetation Change in Central Africa: The Need for an Integrated Management Framework for Forests and Savannas
peer reviewedTropical forests and savannas are the main biomes in sub-Saharan Africa, covering most of the continent. Collectively they offer important habitat for biodiversity and provide multiple ecosystem services. Considering their global importance and the multiple sustainability challenges they face in the era of the Anthropocene, this chapter undertakes a comprehensive analysis of the past, present, and future vegetation patterns in central African forests and savannas. Past changes in climate, vegetation, land use, and human activity have affected the distribution of forests and savannas across central Africa. Currently, forests form a continuous block across the wet and moist areas of central Africa, and are characterized by high tree cover (>90% tree cover). Savannas and woodlands have lower tree cover (<40% tree cover), are found in drier sites in the north and south of the region, and are maintained by frequent fires. Recent tree cover loss (2000–2015) has been more important for forests than for savannas, which, however, reportedly experienced woody encroachment. Future cropland expansion is expected to have a strong impact on savannas, while the extent of climatic impacts depends on the actual scenario. We finally identify some of the policy implications for restoring ecosystems, expanding protected areas, and designing sustainable ecosystem management approaches in the region
Acid Precipitation
While acid precipitation has been the subject of debate within the scientific community for over a decade, recent events, such as President Reagan's endorsement of a $5 billion "clean-coal" technology research program, passage of emissions reduction legislation by the House Subcommittee on Health and the Environment, and the release of major reports such as the National Research Council's "Acid Deposition: Long-Term Trends," have propelled the issue into a national public spotlight. This paper examines the current status of scientific
research on acid precipitation in the U.S. and the effects on water quality