How explicit are the barriers to failure in safety arguments?

Safety cases embody arguments that demonstrate how safety properties of a system are upheld. Such cases implicitly document the barriers that must exist between hazards and vulnerable components of a system. For safety certification, it is the analysis of these barriers that provide confidence in the safety of the system. The explicit representation of hazard barriers can provide additional insight for the design and evaluation of system safety. They can be identified in a hazard analysis to allow analysts to reflect on particular design choices. Barrier existence in a live system can be mapped to abstract barrier representations to provide both verification of barrier existence and a basis for quantitative measures between the predicted barrier behaviour and performance of the actual barrier. This paper explores the first stage of this process, the binding between explicit mitigation arguments in hazard analysis and the barrier concept. Examples from the domains of computer-assisted detection in mammography and free route airspace feasibility are examined and the implications for system certification are considered

A strategic framework to support the implementation of citizen science for environmental monitoring. Final report to SEPA

In this report we provide a decision framework that can be used to guide whether and when to use a citizen science approach for environmental monitoring. Before using the decision framework we recommend that five precursors to a citizen science approach are considered

Choosing and using citizen science: a guide to when and how to use citizen science to monitor biodiversity and the environment

Here we aim to provide guidance to support people considering using a citizen science approach, especially (but not necessarily restricted to) monitoring biodiversity and the environment in the UK. It will help you decide whether citizen science is likely to be useful, and it will help you decide which broad approach to citizen science is most suitable for your question or activity. This guide does not cover the practical detail of developing a citizen science project. That information is provided in the ‘Guide to Citizen Science’ (Tweddle et al., 2012)

The influence of the R47H triggering receptor expressed on myeloid cells 2 variant on microglial exosome profiles

Variants in the triggering receptor expressed on myeloid cells 2 gene are linked with an increased risk of dementia, in particular the R47H^{het} triggering receptor expressed on myeloid cells 2 variant is linked to late-onset Alzheimer’s disease. Using human induced pluripotent stem cells-derived microglia, we assessed whether variations in the dynamics of exosome secretion, including their components, from these cells might underlie some of this risk. We found exosome size was not altered between common variant controls and R47H^{het} variants, but the amount and constitution of exosomes secreted were different. Exosome quantities were rescued by incubation with an ATP donor or with lipids via a phosphatidylserine triggering receptor expressed on myeloid cells 2 ligand. Following a lipopolysaccharide or phagocytic cell stimulus, exosomes from common variant and R47H^{heht} microglia were found to contain cytokines, chemokines, APOE and triggering receptor expressed on myeloid cells 2. Differences were observed in the expression of CCL22, IL-1β and triggering receptor expressed on myeloid cells 2 between common variant and R47H^{het} derived exosomes. Furthermore unlike common variant-derived exosomes, R47H^{het} exosomes contained additional proteins linked to negative regulation of transcription and metabolic processes. Subsequent addition of exosomes to stressed neurones showed R47H^{het}derived exosomes to be less protective. These data have ramifications for the responses of microglia in Alzheimer’s disease and may point to further targets for therapeutic intervention

Differential stimulation of pluripotent stem cell-derived human microglia leads to exosomal proteomic changes affecting neurons

Microglial exosomes are an emerging communication pathway, implicated in fulfilling homeostatic microglial functions and transmitting neurodegenerative signals. Gene variants of triggering receptor expressed on myeloid cells-2 (TREM2) are associated with an increased risk of developing dementia. We investigated the influence of the TREM2 Alzheimer’s disease risk variant, R47Hhet, on the microglial exosomal proteome consisting of 3019 proteins secreted from human iPS-derived microglia (iPS-Mg). Exosomal protein content changed according to how the iPS-Mg were stimulated. Thus lipopolysaccharide (LPS) induced microglial exosomes to contain more inflammatory signals, whilst stimulation with the TREM2 ligand phosphatidylserine (PS+) increased metabolic signals within the microglial exosomes. We tested the effect of these exosomes on neurons and found that the exosomal protein changes were functionally relevant and influenced downstream functions in both neurons and microglia. Exosomes from R47Hhet iPS-Mg contained disease-associated microglial (DAM) signature proteins and were less able to promote the outgrowth of neuronal processes and increase mitochondrial metabolism in neurons compared with exosomes from the common TREM2 variant iPS-Mg. Taken together, these data highlight the importance of microglial exosomes in fulfilling microglial functions. Additionally, variations in the exosomal proteome influenced by the R47Hhet TREM2 variant may underlie the increased risk of Alzheimer’s disease associated with this variant

Adam Smith and Colonialism

In the context of debates about liberalism and colonialism, the arguments of Adam Smith have been taken as illustrative of an important line of anti-colonial liberal thought. The reading of Smith presented here challenges this interpretation. It argues that Smith’s opposition to colonial rule derived largely from its impact on the metropole, rather than on its impact on the conquered and colonised; that Smith recognised colonialism had brought ‘improvement’ in conquered territories and that Smith struggled to balance recognition of moral diversity with a universal moral framework and a commitment to a particular interpretation of progress through history. These arguments have a wider significance as they point towards some of the issues at stake in liberal anti-colonial arguments more generally