On the Use of Marker Strategy Design to Detect Predictive Marker Effect in Cancer Immunotherapy

Indiana University-Purdue University Indianapolis (IUPUI)The marker strategy design (MSGD) has been proposed to assess and validate predictive markers for targeted therapies and immunotherapies. Under this design, patients are randomized into two strategies: the marker-based strategy, which treats patients based on their marker status, and the non-marker-based strategy, which randomizes patients into treatments independent of their marker status in the same way as in a standard randomized clinical trial. The strategy effect is then tested by comparing the response rate between the two strategies and this strategy effect is commonly used to evaluate the predictive capability of the markers. We show that this commonly used between-strategy test is flawed, which may cause investigators to miss the opportunity to discover important predictive markers or falsely claim an irrelevant marker as predictive. Then we propose new procedures to improve the power of the MSGD to detect the predictive marker effect. One is based on a binary response endpoint; the second is based on survival endpoints. We conduct simulation studies to compare the performance of the MSGD with the widely used marker stratified design (MSFD). Numerical studies show that the MSGD and MSFD has comparable performance. Hence, contrary to popular belief that the MSGD is an inferior design compared with the MSFD, we conclude that using the MSGD with the proposed tests is an efficient and ethical way to find predictive markers for targeted therapies

The role of economics in ecosystem based management:The case of the EU Marine Strategy Framework Directive; first lessons learnt and way forward

The EU Marine Strategy Framework Directive (MSFD) sets out a plan of action relating to marine environmental policy and in particular to achieving ‘good environmental status’ (GES) in European marine waters by 2020. Article 8.1 (c) of the Directive calls for ‘an economic and social analysis of the use of those waters and of the cost of degradation of the marine environment’. The MSFD is ‘informed’ by the Ecosystem Approach to management, with GES interpreted in terms of ecosystem functioning and services provision. Implementation of the Ecosystem Approach is expected to be by adaptive management policy and practice. The initial socio-economic assessment was made by maritime EU Member States between 2011 and 2012, with future updates to be made on a regular basis. For the majority of Member States, this assessment has led to an exercise combining an analysis of maritime activities both at national and coastal zone scales, and an analysis of the non-market value of marine waters. In this paper we examine the approaches taken in more detail, outline the main challenges facing the Member States in assessing the economic value of achieving GES as outlined in the Directive and make recommendations for the theoretically sound and practically useful completion of the required follow-up economic assessments specified in the MSFD

Editorial: Bridging the gap between policy and science in assessing the health status of marine ecosystems

Human activities,both established and emerging, increasingly affect the provision of marine ecosystem services that deliver societal and economic benefits. Monitoring the status of marine ecosystems and determining how human activities change their capacity to sustain benefits for society requires an evidence-based Integrated Ecosystem Assessment approach that incorporates knowledge of ecosystem functioning and services).Although,there are diverse methods to assess the status of individual ecosystem components, none assesses the health of marine ecosystems holistically, integrating information from multiple ecosystem components. Similarly,while acknowledging the availability of several methods to measure single pressures and assess their impacts, evaluation of cumulative effects of multiple pressures remains scarce.Therefore,an integrative assessment requires us to first understand the response of marine ecosystems to human activities and their pressures and then develop innovative, cost-effective monitoring tools that enable collection of data to assess the health status of large marine areas. Conceptually, combining this knowledge of effective monitoring methods with cost-benefit analyses will help identify appropriate management measures to improve environmental status economically and efficiently. The European project DEVOTES (DEVelopment Of innovative Tools for understanding marine biodiversity and assessing good Environmental Status) specifically addressed these topics in order to support policymakers and managers in implementing the European Marine Strategy Framework Directive. Here, we synthesize our main innovative findings, placing these within the context of recent wider research, and identifying gaps and the major future challenges

Assessing costs and benefits of measures to achieve good environmental status in European regional seas: challenges, opportunities, and lessons learnt

The EU Marine Strategy Framework Directive (MSFD) requires Member States to assess the costs and benefits of Programmes of Measures (PoMs) put in place to ensure that European marine waters achieve Good Environmental Status by 2020. An interdisciplinary approach is needed to carry out such an assessment whereby economic analysis is used to evaluate the outputs from ecological analysis that determines the expected effects of such management measures. This paper applies and tests an existing six-step approach to assess costs and benefits of management measures with potential to support the overall goal of the MSFD and discusses a range of ecological and economic analytical tools applicable to this task. Environmental cost-benefit analyses are considered for selected PoMs in three European case studies: Baltic Sea (Finland), East Coast Marine Plan area (UK), and the Bay of Biscay (Spain). These contrasting case studies are used to investigate the application of environmental cost-benefit analysis (CBA) including the challenges, opportunities and lessons learnt from using this approach. This paper demonstrates that there are opportunities in applying the six-step environmental CBA framework presented to assess the impact of PoMs. However, given demonstrated limitations of knowledge and data availability, application of other economic techniques should also be considered (although not applied here) to complement the more formal environmental CBA approach

What is marine biodiversity? Towards common concepts and their implications for assessing biodiversity status

Biodiversity' is one of the most common keywords used in environmental sciences, spanning from research to management, nature conservation, and consultancy. Despite this, our understanding of the underlying concepts varies greatly, between and within disciplines as well as among the scientists themselves. Biodiversity can refer to descriptions or assessments of the status and condition of all or selected groups of organisms, from the genetic variability, to the species, populations, communities, and ecosystems. However, a concept of biodiversity also must encompass understanding the interactions and functions on all levels from individuals up to the whole ecosystem, including changes related to natural and anthropogenic environmental pressures. While biodiversity as such is an abstract and relative concept rooted in the spatial domain, it is central to most international, European, and national governance initiatives aimed at protecting the marine environment. These rely on status assessments of biodiversity which typically require numerical targets and specific reference values, to allow comparison in space and/or time, often in association with some external structuring factors such as physical and biogeochemical conditions. Given that our ability to apply and interpret such assessments requires a solid conceptual understanding of marine biodiversity, here we define this and show how the abstract concept can and needs to be interpreted and subsequently applied in biodiversity assessments

Biodiversity hotspots on the Dutch Continental Shelf: a marine strategy framework directive perspective

This report presenst hotspots of biodiversity for benthos, fish, birds, marine mammals and habitats on the Dutch Continental Shelf. These hotspots are based on a spatial application of biodiversity metrics developed in this study for the GES(Good Environmental Status)-descriptor 1 ‘Biological diversity is maintained’ of the Marine Strategy Framework Directive (MSFD) (EU 2008). The choice of the biodiversity metrics is based on the proposed indicators of biodiversity in the Commission Decision (EU 2010). The purpose of this study is to provide insight in possibilities for spatial protection measures in the framework of the MSFD. This report feeds information and ideas into further work for the MSFD in the Netherlands. IMARES has compiled this report for the Dutch Ministry of Economic Affairs, Agriculture and Innovation (Ministry of EL&I) and the Ministry of Infrastructure and the Environment (I&M)

The current cost of avoiding degradation of the Dutch North Sea Environment

Het doel van dit rapport is een overzicht te geven van de kosten die jaarlijks worden uitgegeven om de aantasting van het milieu in het Nederlandse deel van de Noordzee te voorkomen. Dit overzicht kan wor# den gebruikt als indicatie voor de ondergrens van de werkelijke aan de aantasting van het mariene milieu verbonden kosten. Daarnaast geeft dit rapport inzicht in het type maatregelen en wie de kosten hiervan dragen. De uitkomsten van dit rapport kunnen zowel dienen als basis voor een kosteneffectiviteitsstudie, als voor het bepalen van de betaalbaarheid en/of de disproportionaliteit van kosten voor toekomstige Kaderrichtlijn Mariene Strategie (KRM) maatregele

Converting energy from fusion into useful forms

If fusion power reactors are to be feasible, it will still be necessary to convert the energy of the nuclear reaction into usable form. The heat produced will be removed from the reactor core by a primary coolant, which might be water, helium, molten lithium-lead, molten lithium-containing salt, or CO2. The heat could then be transferred to a conventional Rankine cycle or Brayton (gas turbine) cycle. Alternatively it could be used for thermochemical processes such as producing hydrogen or other transport fuels. Fusion presents new problems because of the high energy neutrons released. These affect the selection of materials and the operating temperature, ultimately determining the choice of coolant and working cycle. The limited temperature ranges allowed by present day irradiated structural materials, combined with the large internal power demand of the plant, will limit the overall thermal efficiency. The operating conditions of the fusion power source, the materials, coolant, and energy conversion system will all need to be closely integrated.Comment: 22 pages, 4 figures, Proceedings of the Institution of Mechanical Engineers, Part A: Journal of Power and Energy December 11, 201