Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

A new pattern for historical geography: working with enthusiast communities and public history

This paper argues for the adoption of participatory approaches in historical geography, drawing on the author's experience in working with enthusiast communities in the UK in the context of collaborative research with the Science Museum and ideas of public history and geography.

Scales and voices in World Historical Archaeology

This paper briefly sets the scene for the articles that follow, introducing some key debates that have characterized the recent practice of historical archaeology. The definition of historical archaeology is explored according to parameters of chronology and methodology, drawing a distinction between New World traditions that define the subject as 'post-Columbian' and Old World approaches that establish broader connections with the 'documentary archaeology' of all literate societies. Current issues in European and American historical archaeology are highlighted, including the gradual breakdown of the medieval/post-medieval divide and the call for a global 'modern-world archaeology' to address the 'grand historical narratives' of the period, such as capitalism, economic improvement, and consumerism. The resistance to this global research agenda is explored with reference to archaeologies of diaspora and postcolonialism, which demand local perspectives to explore diversity and meaning. Finally, the innovative use of community archaeology and multi-vocality is introduced, with particular reference to the experimental narratives pursued by American historical archaeologists, in their new role as 'storytellers'.

Introduction: scales and voices in world historical archaeology

This paper briefly sets the scene for the articles that follow, introducing some key debates that have characterized the recent practice of historical archaeology. The definition of historical archaeology is explored according to parameters of chronology and methodology, drawing a distinction between New World traditions that define the subject as 'post-Columbian' and Old World approaches that establish broader connections with the 'documentary archaeology' of all literate societies. Current issues in European and American historical archaeology are highlighted, including the gradual breakdown of the medieval/post-medieval divide and the call for a global 'modern-world archaeology' to address the 'grand historical narratives' of the period, such as capitalism, economic improvement, and consumerism. The resistance to this global research agenda is explored with reference to archaeologies of diaspora and postcolonialism, which demand local perspectives to explore diversity and meaning. Finally, the innovative use of community archaeology and multi-vocality is introduced, with particular reference to the experimental narratives pursued by American historical archaeologists, in their new role as 'storytellers'.

Informal finance and rural finance policy in India: historical and contemporary perspectives

From the 1950s up to the early 1990s the All-India data show an ever-declining share of informal credit in the total outstanding debt of rural households. Contemporaneous micro-level studies, using more qualitative research methodologies, provide evidence that questions the strength of this trend, and more recent All-India credit surveys show, first, a levelling, and then a rise, in the share of rural informal credit in 1990/91 and 2000/01, respectively. By reference to findings of a study of village moneylenders in Rajasthan, the paper notes lessons to be drawn. First, informal financial agents have not disappeared from the rural financial landscape in India. Second, formal-sector financial institutions can learn much about rural financial service needs from the financial products and processes of their informal counterparts. Third, a national survey of informal agents, similar to that of the 1921 Census survey of indigenous bankers and moneylenders, would provide valuable pointers towards policy options for the sector. A recent Reserve Bank of India Report on Moneylender Legislation not only explores incentive mechanisms to better ensure fair practice, but also proposes provision for a new category of loan providers that would explicitly link the rural informal and formal financial sectors.

Foreign direct investment in high-risk environments: an historical perspective

Since the banking crisis of 2008 the global economy is perceived as riskier than before. Firms that cannot manage risks have withdrawn from countries in which they previously invested. These problems are not new. For centuries firms have invested in risky foreign environments, and many of them have succeeded. This paper reviews the risk management strategies of foreign investors. Using archival evidence and secondary sources it distinguishes the different types of risks that investors face and the different strategies by which risks can be managed. It investigates which strategies are used to manage which types of risk.

Breaking the impasse: towards a new regime for international climate governance

The reality of the current international order makes it imperative that a just and effective climate regime balance the historical responsibility of developed countries with the increasing absolute emissions from many developing nations. In this short outlook article, key pillars are proposed for a new international climate architecture that envisions replacing the current annex system with two new annexes –Annex α, for countries with high current emissions and historically high emissions, and Annex β, for countries with high current emissions and historically low emissions. Countries in both annexes would implement legally binding targets under this framework. Additionally, this proposal includes tweaks and revisions to funding and technology transfer mechanisms to correct for weaknesses and inequities under the current Kyoto architecture. The proposed framework stems from a belief that a top-down, international approach to climate policy remains the most effective for ensuring environmental integrity. Given the slow rate of institutional learning, reforming and improving the current system is held as a more efficient course of action than abandoning the progress already achieved. It is argued that the proposed framework effectively accommodates key equity, environmental integrity and political feasibility concerns.