Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial.     

External knowledge search,absorptive capacity and radical innovation in high-technology firms

Open innovation and absorptive capacity are two concepts based on the idea that companies can leverage the knowledge generated externally to improve their innovation performance. The aim of this paper is to analyse the joint effect of open innovation and absorptive capacity on a firm's radical innovation. Open innovation is expressed in terms of external search breadth and depth strategies and absorptive capacity is described by distinguishing between potential and realized absorptive capacity. In order to test our hypotheses, we carried out empirical research in firms operating in high-technology industries. The results indicate that internal routines and processes for absorbing external knowledge help explain radical innovation as they show a significant effect of potential and realized absorptive capacity. Also, there is a moderating effect of absorptive capacity on open innovation. Specifically, potential absorptive capacity exerts a positive effect on the relationship between external search breadth and depth and radical innovation. Realized absorptive capacity moderates the influence of external search breadth. These findings confirm the complementary nature of absorptive capacity and open innovation search strategies on radical innovation.     

Applying kaizen to the schedule in a concurrent environment

Not only ETO (Engineering to Order), but even serial production industry should know how to deal with projects and their schedule: plant commissioning, shutdown, introducing new products and similar circumstances should be managed with adequate planning and resource allocation techniques to create a schedule useful in decision making during the execution. The current complex reality, with evolving technologies and fierce pressure to reach the market as soon as possible, pushes the project managers to use more advanced techniques than waterfall planning, such as agile or lean. It also requires them to take a holistic view and manage concurrent tasks in complex projects. The contributions of this paper are two: the proposal to control specific parallel groups of waterfall activities under uncertain environments, which can lead to iterations and reworks, as a single concurrent Activity Managed by Kanban Methods (AMKM). This activity can be subsequently embedded into traditional scheduling approaches as CPM-PERT. The second contribution is the feasibility of its application in industrial environments due to the affordability of simulation software. Two use cases are shown as evidence. It is not a disruptive proposal, but a kaizen action based on very mature technologies. Finally, it is suggested some improvements to be implemented in Project Management Software due to this ‘kaizen’ proposal.     

International and intercultural issues in English teaching textbooks: the case of Spain

The sociocultural content of foreign language textbooks has become a concern of scholars and practitioners owing to the fact that the traditional emphasis on purely linguistic issues has been expanded to embrace a language in context approach. This paper studies the English‐speaking communities that are described in English language teaching textbooks marketed in Spain. It examines to what extent an international and/or intercultural approach is a constituent element in their design.     

Demographic Shifts in the Czech Republic after 1989: A Second Demographic Transition View

A dramatic change in fertility,family formation and living arrangements tookplace in the Czech Republic over the 1990s. Theestablishment of democracy, profound socialtransformation and transition to the marketeconomy affected the values and demographicbehaviour of the young Czech generation. Thispaper examines whether these demographic shiftscan be interpreted within the framework of thesecond demographic transition. The theoreticalpart discusses the idea of the transition,outlining three distinctive conceptualisations.Two of them – the view of the transition as aprogression of characteristic interrelateddemographic changes and a broader viewstressing the importance of underlyingideational factors – fit the Czech situationvery well. A comparison with the Netherlandsreveals that the onset of the transition in theCzech Republic may be clearly located in thefirst half of the 1990s, lagging two decadesbehind the Netherlands.     

Some results on optimality in models with heteroscedastic errors from partial optimum designs

This paper studies optimum designs for linear models when the errors are heteroscedastic. Sufficient conditions are given in order to obtainD-, A- andE-optimum designs for a complete regression model from partial optimum designs for some sub-parameters. A result about optimality for a complete model from the optimality for the submodels is included. Supported by Junta de Andalucía, research group FQM244.     

Applicability of a Neuroprobabilistic Integral Risk Index for the Environmental Management of Polluted Areas: A Case Study

Recently, we developed a GIS-Integrated Integral Risk Index (IRI) to assess human health risks in areas with presence of environmental pollutants. Contaminants were previously ranked by applying a self-organizing map (SOM) to their characteristics of persistence, bioaccumulation, and toxicity in order to obtain the Hazard Index (HI). In the present study, the original IRI was substantially improved by allowing the entrance of probabilistic data. A neuroprobabilistic HI was developed by combining SOM and Monte Carlo analysis. In general terms, the deterministic and probabilistic HIs followed a similar pattern: polychlorinated biphenyls (PCBs) and light polycyclic aromatic hydrocarbons (PAHs) were the pollutants showing the highest and lowest values of HI, respectively. However, the bioaccumulation value of heavy metals notably increased after considering a probability density function to explain the bioaccumulation factor. To check its applicability, a case study was investigated. The probabilistic integral risk was calculated in the chemical/petrochemical industrial area of Tarragona (Catalonia, Spain), where an environmental program has been carried out since 2002. The risk change between 2002 and 2005 was evaluated on the basis of probabilistic data of the levels of various pollutants in soils. The results indicated that the risk of the chemicals under study did not follow a homogeneous tendency. However, the current levels of pollution do not mean a relevant source of health risks for the local population. Moreover, the neuroprobabilistic HI seems to be an adequate tool to be taken into account in risk assessment processes.