Blood and saliva-derived exomes from healthy Caucasian subjects do not display overt evidence of somatic mosaicism

Somatic mosaicism is a normal occurrence during development in the tissues and organs. As part of establishing a “healthy population “(HP) background or base-line, we investigated whether such mosaicism can be routinely detected in the circulating DNA secured from a rigorously designed healthy human liquid biopsy clinical trial (saliva, blood). We deployed next generation (NG) whole exome sequencing (WES) at median exome coverage rates of 97.2 % (-to-30x) and 70.0 % (-to-100x). We found that somatic mosaicism is not detectable by such standard bulk WES sequencing assays in saliva and blood DNA in 24 normal healthy Caucasians of both sexes from 18 to 60 years of age. We conclude that for circulating DNA using standard WES no novel somatic mutational variants can be detected in protein-coding regions of normal healthy subjects. This implies that the extent within normal tissues of somatic mosaicism must be at a lower level, below the detection threshold, for these circulating DNA WES read depths. © 2020 The Author(s

Seven features of safety in maternity units: a framework based on multisite ethnography and stakeholder consultation

Background: Reducing avoidable harm in maternity services is a priority globally. As well as learning from mistakes, it is important to produce rigorous descriptions of ‘what good looks like’. Objective: We aimed to characterise features of safety in maternity units and to generate a plain language framework that could be used to guide learning and improvement. Methods: We conducted a multisite ethnography involving 401 hours of non-participant observations 33 semistructured interviews with staff across six maternity units, and a stakeholder consultation involving 65 semistructured telephone interviews and one focus group. Results: We identified seven features of safety in maternity units and summarised them into a framework, named For Us (For Unit Safety). The features include: (1) commitment to safety and improvement at all levels, with everyone involved; (2) technical competence, supported by formal training and informal learning; (3) teamwork, cooperation and positive working relationships; (4) constant reinforcing of safe, ethical and respectful behaviours; (5) multiple problem-sensing systems, used as basis of action; (6) systems and processes designed for safety, and regularly reviewed and optimised; (7) effective coordination and ability to mobilise quickly. These features appear to have a synergistic character, such that each feature is necessary but not sufficient on its own: the features operate in concert through multiple forms of feedback and amplification. Conclusions: This large qualitative study has enabled the generation of a new plain language framework—For Us—that identifies the behaviours and practices that appear to be features of safe care in hospital-based maternity units

The age of smart cards: an exploratory investigation of the sociotechnical factors influencing smart card innovation (1974-1996)

This thesis breaks new ground by providing the first detailed study of smart card innovation during its first twenty years (1974-1996). The overall aim is to apply sociotechnical principles to further our understanding of the innovation process as it relates to smart card technology. By using a sociotechnical framework, this study also seeks to illustrate the limitations of conventional innovation theory when applied to new information technologies such as smart card: The central thesis posited, is that to develop our understanding of the underlying innovation processes that have occurred during the development of this new information technology, it is necessary to study the interactions between three actors that have all appeared to play a role in the process of smart card innovation. These are smart card technology; the potential users and the organisations. However, in stating this, it is also important to realize that one tacit assumption underlying the work reported here is that new technologies are only adopted if the technological parameters (technology focus), the market needs (user focus) and the entrepreneurs (organisational focus) meet. At a more abstract level, the work has also endeavoured to consider whether a sociotechnical approach applied as a framework for understanding the process of innovation for smart card is, in fact, a reasonable and useful paradigm for developing our understanding from both a theoretical and applied perspective. Thus the multidisciplinary process approach adopted is not intended to lead to a complete alternative theory: nor is it intended to be merely a synthesis. What the current work has achieved, is to provide the very first insights into the understanding of smart card innovation. The sociotechnical framework adopted as a theoretical organiser and, which emphasises the role of the user, has also served to highlight the need for a multidisciplinary approach to develop our understanding of smart card innovation. The view upheld is that the paradigm emerging from these analyses based on traditional innovation thought, both demands and empowers the view of smart card innovation as a sociotechnical process. One of the main outcomes has been to demonstrate that smart card innovation provides a case in point highlighting the benefits of adopting a broad and evolutionary approach to innovation and based on a sociotechnical framework. This is in agreement with recent paradigm shifts in technology innovation thought. For the practitioner, these findings also illuminate new possibilities for the development theoretically informed smart card systems, thus placing the smart card design team in a position to significantly and positively influence future smart card innovation patterns

Medical educators response to a web-based nutrition implementation toolkit (WNCIT) for entry level medical courses

Meeting abstract

Nature of Acquired Immune Responses, Epitope Specificity and Resultant Protection from SARS-CoV-2

The primary global response to the SARS-CoV-2 pandemic has been to bring to the clinic as rapidly as possible a number of vaccines that are predicted to enhance immunity to this viral infection. While the rapidity with which these vaccines have been developed and tested (at least for short-term efficacy and safety) is commendable, it should be acknowledged that this has occurred despite the lack of research into, and understanding of, the immune elements important for natural host protection against the virus, making this endeavor a somewhat unique one in medical history. In contrast, as pointed out in the review below, there were already important past observations that suggested that respiratory infections at mucosal surfaces were susceptible to immune clearance by mechanisms not typical of infections caused by systemic (blood-borne) pathogens. Accordingly, it was likely to be important to understand the role for both innate and acquired immunity in response to viral infection, as well as the optimum acquired immune resistance mechanisms for viral clearance (B cell or antibody-mediated, versus T cell mediated). This information was needed both to guide vaccine development and to monitor its success. We have known that many pathogens enter into a quasi-symbiotic relationship with the host, with each undergoing sequential change in response to alterations the other makes to its presence. The subsequent evolution of viral variants which has caused such widespread concern over the last 3–6 months as host immunity develops was an entirely predictable response. What is still not known is whether there will be other unexpected side-effects of the deployment of novel vaccines in humans which have yet to be characterized, and, if so, how and if these can be avoided. We conclude by remarking that to ignore a substantial body of well-attested immunological research in favour of expediency is a poor way to proceed

Additional file 2: of Protocol-based management of older adults with hip fractures in Delhi, India: a feasibility study

Patient and carer focus group discussion. (DOCX 780 kb