Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

The institutionalization of knowledge transfer activities within industry–university collaborative ventures

Due to the changing competitive landscape, organizations must increasingly focus on acquiring external knowledge to advance new technologies. This study examines the institutionalization of knowledge transfer activities between industrial firms and university research centers. Data were collected from 189 firms collaborating with 21 university research centers in the US. Results show that knowledge transfer activities are facilitated when industrial firms have more mechanistic structures, cultures that are more stable and direction-oriented, and when the firm is more trusting of its university research center partner. Implications for both industry and universities, including their effect on firm performance, are discussed.     

Does exposure to a traumatic event make organizations resilient?

Why do some organizations bounce-back from traumatic events more quickly than others? While the research on organizations offers extensive insights on recovery from economic or technological shocks, there is limited understanding of how organizations recover from life-threatening events such as terrorist attacks. In this study, we build on the research on resilience and argue that organizational recovery from a traumatic event is informed by the perception of threat. Higher perception of threat increases inter-organizational collaboration and the care associated with the deployment of slack as well as to learning. We tested our arguments with a sample of US and non-US firms before and after the 9/11 terrorist attacks and found that, due to spatial proximity, US firms’ higher perception of threat led to a larger increase in the frequency of inter-organizational alliances than that of non-US firms. This preference was more frequently directed towards local partners and demonstrated a distinct emphasis on slack and learning. Contrary to conventional wisdom, our findings suggest that organizational resilience in the face of a traumatic event benefits not from immunity but from spatial proximity to the threat. Proximity increases the perception of threat, and with it, the impetus for adaptation.     

Assessment of systemic greenness: a case study of tyre manufacturing unit

Abstract

In this paper, we develop an assessment framework to evaluate the systemic greenness of a tyre manufacturing unit by capturing the interactions between the green practices implemented. By reviewing the existing literature, we propose a stakeholder-based green practices framework comprising of operation strategy practices, process practices, employee practices, regulatory practices, customer practices, competition practices, social practices, and supplier practices. The empirical data on the interactions of green practices between and within stakeholders are collected by conducting a detailed case study of a large radial tyre manufacturing unit in India. We use graph-theoretic approach to incorporate the interactions between different green practices and assess the systemic greenness of the case organisation. Based on the systemic greenness attained, we rank the green practices within stakeholders and also between the stakeholders. We conduct scenario analysis to develop a systemic greenness index and a scale to assist practitioners in evaluating and benchmarking the greenness performance. We also discuss implications for theory and practice along with the inherent limitations.     

Inapproximability results for the lateral gene transfer problem

This paper concerns the Lateral Gene Transfer Problem. This minimization problem, defined by Hallett and Lagergren (2001), is that of finding the most parsimonious lateral gene transfer scenario for a given pair of gene and species trees. Our main results are the following:

An empirical study of the impact of firm resources on alliance governance structures

Alliances between smaller biotechnology firms and larger pharmaceutical firms are the backbone of new product development strategies within the pharmaceutical industry. While pharmaceutical firms seek access to new technologies and products, small biotechnology firms depend on these alliance relationships to access key resources such as financing and downstream capabilities because they typically do not have the resources needed in-house to successfully commercialize their products. In this study, we investigate the governance structure of these alliance relationships arguing that the more resource rich a biotechnology firm is, in terms of technical, commercial, and social capital, the less likely it is to give up equity to an alliance partner. Results suggest that greater biotech patent quality, cash position, and alliance credibility impact the type of governance structure that is chosen by the alliance partners and therefore the extent of control that the biotechnology firm is willing to give up in the relationship.     

Well London: Results of a Community Engagement Approach to Improving Health Among Adolescents from Areas of Deprivation in London

This article reports findings among adolescents of the impact of Well London, a program of wellbeing interventions delivered across 20 deprived neighbourhoods of London using a community engagement model. Twelve hundred and fifty-four adolescents were surveyed from matched intervention and control areas. There was no significant intervention effect on the main outcome measures: unhealthy eating, physical activity, and mental health. Factors influencing the results may include the possibility that the communities defined by the cluster randomized controlled trial (CRCT) were not an accurate reflection of the adolescent’s natural community, and interactions within the school environment in particular could have led to a dilution of effect.     

Coastal settlement patterns and exposure to sea-level rise in the Jaffna Peninsula,Sri Lanka

The Jaffna Peninsula in Sri Lanka has a generally flat topography with a median elevation of 2.72 m, and thus faces a high risk from sea-level rise that has the potential to have adverse impacts on the livelihoods of coastal communities. Understanding these risks and identifying the regions that could be adversely impacted is critical for planning future settlements and developing preventative protocols where possible. The aim of this study was to analyze the exposure of coastal settlements of the Jaffna Peninsula to climate risks, particularly to sea-level rise, and to identify the areas that are likely to be impacted under different sea-level rise scenarios. Raster-based sea-level rise modeling was performed with a digital elevation model produced with topographic contours and spot heights. The spatial distribution of individual residential houses for the entire Jaffna Peninsula was obtained through manual digitization using virtual globe platforms and high-resolution satellite images, and the houses exposed to inundation under various Representative Concentration Pathways from 2025 to 2100 were identified. The results showed that a majority (55.5%) of the residential buildings in the Jaffna Peninsula are located within 3 m above sea level. Approximately 5554 (5.6%) of the houses were projected to be inundated by 2100, and this projection increased to approximately 25,074 (25.4%) under high tide scenarios. This study highlights the coastal communities with a high level of exposure to coastal inundation where adaptation planning is essential. These results provide insights for coastal managers and policy makers for future planning of new settlements and urban expansion.

     

Pro-environmental behaviours and attitudes are associated with health,wellbeing and life satisfaction in multiple occupancy households in the UK Household Longitudinal Study

Population and Environment - Pro-environmental behaviours (PEBs) and attitudes (PEAs) may influence different domains of health and wellbeing through several mechanisms. The household plays an...     

Capacity Planning and Allocation for Web‐Based Applications

Motivated by the technology division of a financial services firm, we study the problem of capacity planning and allocation for Web‐based applications. The steady growth in Web traffic has affected the quality of service (QoS) as measured by response time (RT), for numerous e‐businesses. In addition, the lack of understanding of system interactions and availability of proper planning tools has impeded effective capacity management. Managers typically make decisions to add server capacity on an ad hoc basis when systems reach critical response levels. Very often this turns out to be too late and results in extremely long response times and the system crashes. We present an analytical model to understand system interactions with the goal of making better server capacity decisions based on the results. The model studies the relationships and important interactions between the various components of a Web‐based application using a continuous time Markov chain embedded in a queuing network as the basic framework. We use several structured aggregation schemes to appropriately represent a complex system, and demonstrate how the model can be used to quickly predict system performance, which facilitates effective capacity allocation decision making. Using simulation as a benchmark, we show that our model produces results within 5% accuracy at a fraction of the time of simulation, even at high traffic intensities. This knowledge helps managers quickly analyze the performance of the system and better plan server capacity to maintain desirable levels of QoS. We also demonstrate how to utilize a combination of dedicated and shared resources to achieve QoS using fewer servers.