How important is ‘implementation science’ for national genomics policy?

The traditional translation pathway of ‘bench- to-bedside’ will not be enough to integrate genomics into routine clinical care. It requires the use of validated and systematic ‘implementation science’ methods. Within the pipeline of evidence-based translation of new technologies, implementation science is the phase that informs policy regarding the appropriateness, adoption, feasibility, acceptability, fidelity, penetration, and sustainability of technologies being transferred from research settings into the real world. Without implementation science, barriers can emerge unchecked and key drivers neglected. Health services researchers now have a large knowledge base which identifies barriers and drivers for implementation of new technologies into healthcare

The rise of rapid implementation: a worked example of solving an existing problem with a new method by combining concept analysis with a systematic integrative review

Background The concept of rapid implementation has emerged in the literature recently, but without a precise definition. Further exploration is required to distinguish the concept’s unique meanings and significance from the perspective of implementation science. The study clarifies the concept of rapid implementation and identifies its attributes, antecedents, and consequences. We present a theoretical definition of rapid implementation to clarify its unique meaning and characteristics. Methods Rodgers evolutionary concept analysis method, combined with a systematic integrative review, were used to clarify the concept of rapid implementation. A comprehensive search of four databases, including EMBASE, MEDLINE, SCOPUS, and WEB OF SCIENCE was conducted, as well as relevant journals and reference lists of retrieved studies. After searching databases, 2442 papers were identified from 1963 to 2019; 24 articles were found to fit the inclusion criteria to capture data on rapid implementation from across healthcare settings in four countries. Data analysis was carried out using descriptive thematic analysis. Results The results locate the introduction of rapid implementation, informed by implementation science. Guidance for further conceptualisation to bridge the gap between research and practice and redefine rigour, adapting methods used (current approaches, procedures and frameworks), and challenging clinical trial design (efficacy-effectiveness-implementation pipeline) is provided. Conclusions It is possible that we are on the cusp of a paradigm shift within implementation brought about by the need for faster results into practice and policy. Researchers can benefit from a deeper understanding of the rapid implementation concept to guide future implementation of rapid actionable results in clinical practice

Discovery of proteins and pathways contributing to TDP-43-mediated neurodegeneration in a novel transgenic mouse model of disease

Theoretical thesis.Bibliography: pages 225-236.1. Introduction -- 2. Study topic and claims -- 3. Methods and materials -- 4. Results -- 5. Discussion.Motor neuron disease (MND)/amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease caused by progressive loss of motor neurons controlling movement. The main pathology exhibited by 97% of ALS cases is the aggregation of the RNA/DNA-binding protein TDP-43 within the cytoplasm of affected neurons. Although ALS pathology is characterised by TDP-43 accumulation, it is not understood how this dysfunction causes disease, meaning that it has not been possible to design disease-modifying therapeutics. To combat this issue, a new transgenic mouse model was created to develop the disease as presented in humans which exhibits both pathology as well as a disease phenotype very similar to human ALS. Using the new transgenic mouse model, a large-scale advanced quantitative mass spectrometry (SWATH-MS) study was performed to discover the protein changes involved in TDP-43-mediated pathogenesis. Mass spectrometry results were analysed using several methods ranging from singular protein analysis (Uniprot), to comprehensive analyses (Ingenuity Pathway Analysis). Quantitative immunoblotting and immunofluorescence was used to validate mass spectrometry results. Identified the proteins and pathways which changed during disease course within NLS TDP-43 mice model of ALS. Two key proteins, COQ9 and IMA3, which are involved in known mechanisms of ALS pathogenesis were validated using immunoblotting. In addition, the canonical pathways, upstream regulators and biological function involved in rNLS TDP-43 pathology were comprehensively identified. This study provides important insights into TDP-43-mediated ALS neurodegeneration.1 online resource (265 pages