Treatment allocation strategies for umbrella trials in the presence of multiple biomarkers: A comparison of methods

Umbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers – equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker-guided umbrella trial. We define the pairings representing the pre-trial expectations on efficacy as linked pairs, and the other biomarker-treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment-biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre-specified treatment-biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre-specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.     

Civil religion and secularization: Ideological revitalization in post-revolutionary communist systems

Conventional analyses of secularization typically deal with revealed religions and the increasing disenchantment of their adherents with revealed religious doctrines under conditions of rapid industrialization and urbanization. Very little research, however, has dealt with the rise and decline of religiousity or the impact of secularization in social systems organized around a civil religion. This investigation approaches the development of the Bolshevik party in the Soviet Union as an example of a civil religious movement to test Weber's notions of enchantment and disenchantment against the experience of devoted party activists in order to see how increasing industrialization has influenced the civil religion of Marxism-Leninism and the behavior of individual followers of Marxism-Leninism. Hence, this analysis seeks to discover whether or not a dynamic of secularization, perhaps akin to the growing disenchantment among devoted Protestants from the sixteenth through the nineteenth centuries as discussed by Weber, might be found in post-revolutionary communist societies, like the presentday USSR. If such a dynamic of secularization does exist, then the question of civil religious revivalism, or revitalization movements, will be addressed to consider how and where such revivalistic movements might develop within post-revolutionary, secularized communist systems.     

Using knowledge within small and medium-sized firms: A systematic review of the evidence

This paper provides a systematic review of the literature on how small and medium-sized enterprises (SMEs) use and acquire knowledge. The review was undertaken as part of the Economic and Social Research Council's Evolution of Business Knowledge Programme. The paper describes the systematic review protocol and provides a detailed explanation of the methods used. From the review, it is evident that SME knowledge research concentrates primarily on the acquisition and use of knowledge, treating it as an asset that is transferred by routines. The findings suggest that research is focused in three main areas. First, on the influence and abilities of the entrepreneur to extract, use and develop knowledge resources. Secondly, on firm-wide systems and the social capital that facilitates knowledge exploration and exploitation. Thirdly, on the provision of knowledge and learning experiences through government policy. From a practical perspective, the review concludes that policies encouraging entrepreneurship and economic regeneration need to be more flexible and sensitive to the often complex contexts within which knowledge is used by SMEs. From a research perspective, and given the flexible, opportunity-oriented and often novel nature of SMEs identified in these studies, there is a need to consider the relational and embedded qualities of knowledge by which these characteristics are framed; qualities that resist conceptualization as some form of separable, material asset.     

基本面因素与人民币均衡汇率

测算方法的差异使得对人民币均衡汇率水平的不同研究的测度结果大相径庭。本文借鉴新近研究,引入生产率和国外净资产变量,采用经常账户缺口法、基本行为均衡方法的误差修正模型和ML-ARCH模型测度了人民币汇率的均衡区间;并探讨了决定均衡汇率变化的基本面因素。结果证实人民币被低估的水平并不十分显著,生产率的提升、贸易条件变化和增长导向的经济发展模式和外汇储备是决定均衡汇率变化趋势的关键基本面因素;均衡汇率变化的估值效应能够显著影响国外净资产水平。     

Socioeconomic Vulnerability and Adaptation to Environmental Risk: A Case Study of Climate Change and Flooding in Bangladesh

In this article we investigate the complex relationship between environmental risk, poverty, and vulnerability in a case study carried out in one of the poorest and most flood-prone countries in the world, focusing on household and community vulnerability and adaptive coping mechanisms. Based upon the steadily growing amount of literature in this field we develop and test our own analytical model. In a large-scale household survey carried out in southeast Bangladesh, we ask almost 700 floodplain residents living without any flood protection along the River Meghna about their flood risk exposure, flood problems, flood damage, and coping mechanisms. Novel in our study is the explicit testing of the effectiveness of adaptive coping strategies to reduce flood damage costs. We show that, households with lower income and less access to productive natural assets face higher exposure to risk of flooding. Disparity in income and asset distribution at community level furthermore tends to be higher at higher risk exposure levels, implying that individually vulnerable households are also collectively more vulnerable. Regarding the identification of coping mechanisms to deal with flood events, we look at both the ex ante household level preparedness for flood events and the ex post availability of community-level support and disaster relief. We find somewhat paradoxically that the people that face the highest risk of flooding are the least well prepared, both in terms of household-level ex ante preparedness and community-level ex post flood relief.     

Robust analogs to the coefficient of variation

The coefficient of variation (CV) is commonly used to measure relative dispersion. However, since it is based on the sample mean and standard deviation, outliers can adversely affect it. Additionally, for skewed distributions the mean and standard deviation may be difficult to interpret and, consequently, that may also be the case for the CV. Here we investigate the extent to which quantile-based measures of relative dispersion can provide appropriate summary information as an alternative to the CV. In particular, we investigate two measures, the first being the interquartile range (in lieu of the standard deviation), divided by the median (in lieu of the mean), and the second being the median absolute deviation, divided by the median, as robust estimators of relative dispersion. In addition to comparing the influence functions of the competing estimators and their asymptotic biases and variances, we compare interval estimators using simulation studies to assess coverage.     

The practices of collective action: Practice theory,sustainability transitions and social change

Developing theory for understanding social transformation is essential for environmental sustainability, yet mainstream accounts of collective action neglect the dynamics of daily life. Theories of practice have proved generative for the study of sustainable consumption but struggle to accommodate the roles of collective actors, strategic action and purposive collective projects in social change. In response, this paper develops a practice theoretical account of collective action pertinent to processes of large scale social change, with specific focus on transitions towards sustainability. We consider three ideal types of collective—bureaucratic organisations, groupings and latent networks—and, drawing on existing social theoretical resources that are ontologically compatible with a practice account, explore the kinds of practices and arrangements which compose them. Processes concerning strategy, bureaucracy, management, social worlds and collective identity are identified as important combinations of practices and arrangements. We suggest a key contribution of practice theory has been to identify a type of collective action we call dispersed collective activity, and we suggest how this type of activity may give rise to collectives. We conclude by suggesting further development for the realisation of the project's contribution to the analysis of sustainability transitions.