Precompetitive consensus building to facilitate the use of digital health technologies to support Parkinson Disease drug development through regulatory science

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies

Does biodiversity increase spatial stability in plant community biomass?

We tested the hypothesis that biodiversity decreases the spatial variability of biomass production between subplots taken within experimental grassland plots. Our findings supported this hypothesis if functional diversity (weighted Rao's Q) was considered. Further analyses revealed that diversity in rooting depth and clonal growth form were the most important components of functional diversity stabilizing productivity. Using species or functional group richness as diversity measures there was no significant effect on spatial variability of biomass production, demonstrating the importance of the biodiversity component considered. Moreover, we found a significant increase in spatial variability of productivity with decreasing size of harvested area, suggesting small-scale heterogeneity as an important driver. The ability of diverse communities to stabilize biomass production across spatial heterogeneity may be due to complementary use of spatial niches. Nevertheless, the positive effect of functional diversity on spatial stability appears to be less pronounced than previously reported effects on temporal stability

Separating the concerns of distributed deployment and dynamic composition in internet application systems

The Internet is currently evolving from a global information network into a distributed application system. For example, some Internet applications are based on executing remote services which have been previously installed on possibly multiple Internet nodes, whereas parts of other Internet applications are dynamically moved from several remote nodes to be executed on a single node. In this paper, we focus on the related problem of how the parts of an Internet application that have been independently deployed on multiple Internet nodes can be transparently located, seamlessly retrieved and dynamically composed on a particular node by request. Vie propose a novel deployment and composition approach using so called modules and module federations and show how to separate the logical application composition from the physical module deployment. The realization of our proposal in Java and C++ is presented and the use of the approach in ongoing research projects is demonstrated