Designing high-quality implementation research: development, application, feasibility and preliminary evaluation of the implementation science research development (ImpRes) tool and guide

Background:  Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. Methods:  A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process of reviewing the literature and expert input informed the development and content of the tool. Once consensus had been reached, specialist expert input was sought on involving and engaging patients/service users; and economic evaluation. ImpRes was then applied to 15 implementation and improvement science projects across the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, a research organisation in London, UK. Researchers who applied the ImpRes tool completed an 11-item questionnaire evaluating its structure, content and usefulness. Results:  Consensus was reached on ten implementation science domains to be considered when designing implementation research. These include implementation theories, frameworks and models, determinants of implementation, implementation strategies, implementation outcomes and unintended consequences. Researchers who used the ImpRes tool found it useful for identifying project areas where implementation science is lacking (median 5/5, IQR 4–5) and for improving the quality of implementation research (median 4/5, IQR 4–5) and agreed that it contained the key components that should be considered when designing implementation research (median 4/5, IQR 4–4). Qualitative feedback from researchers who applied the ImpRes tool indicated that a supplementary guide was needed to facilitate use of the tool. Conclusions:  We have developed a feasible and acceptable tool, and supplementary guide, to facilitate consideration and incorporation of core principles and concepts of implementation science in applied health implementation research. Future research is needed to establish whether application of the tool and guide has an effect on the quality of implementation research

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P< 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (rS= 0.20, P< 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells

Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells

Social distancing enhanced automated optimal design of physical spaces in the wake of the COVID-19 pandemic

NoAs the COVID-19 pandemic unfolds, manually enhanced ad-hoc solutions have helped the physical space designers and decision makers to cope with the dynamic nature of space planning. Due to the unpredictable nature by which the pandemic is unfolding, the standard operating procedures also change, and the protocols for physical interaction require continuous reconsideration. Consequently, the development of an appropriate technological solution to address the current challenge of reconfiguring common physical environments with prescribed physical distancing measures is much needed. To do this, we propose a design optimization methodology which takes the dimensions, as well as the constraints and other necessary requirements of a given physical space to yield optimal redesign solutions on the go. The methodology we propose here utilizes the solution to the well-known mathematical circle packing problem, which we define as a constrained mathematical optimization problem. The resulting optimization problem is solved subject to a given set of parameters and constraints – corresponding to the requirements on the social distancing criteria between people and the imposed constraints on the physical spaces such as the position of doors, windows, walkways and the variables related to the indoor airflow pattern. Thus, given the dimensions of a physical space and other essential requirements, the solution resulting from the automated optimization algorithm can suggest an optimal set of redesign solutions from which a user can pick the most feasible option. We demonstrate our automated optimal design methodology by way of a number of practical examples, and we discuss how this framework can be further taken forward as a design platform that can be implemented practically.University of Bradford's COVID-19 Response Fund, the Spanish Ministry of Science, Innovation, and Universities (Computer Science National Program) under grant #TIN2017-89275-Rof the Agencia Estatal de Investigacion and European Funds (AEI/FEDER, UE

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Information Warfare : A Philosophical Perspective

This paper focuses on Information Warfare – the warfare characterised by the use of information and communication technologies. This is a fast growing phenomenon, which poses a number of issues ranging from the military use of such technologies to its political and ethical implications. The paper presents a conceptual analysis of this phenomenon with the goal of investigating its nature. Such an analysis is deemed to be necessary in order to lay the groundwork for future investigations into this topic, addressing the ethical problems engendered by this kind of warfare. The conceptual analysis is developed in three parts. First, it delineates the relation between Informational Warfare and the Information revolution. It then focuses attention on the effects that the diffusion of this phenomenon has on the concepts of state and war. On the basis of this analysis, a definition of Information Warfare is provided as a phenomenon not necessarily sanguinary and violent, and rather transversal concerning the environment in which it is waged, the way it is waged and the ontological and social status of its agents. The paper concludes by taking into consideration Just War Theory and the problems arising from its application to the case of Informational Warfare.Peer reviewe