‘Who? Me. A Memoir’ Donald Leslie Shaw (1930–2017)

No abstract available

Understanding the Dynamics of Gene Regulatory Systems : Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms

Peer reviewedPublisher PD

Symbolic and analytic techniques for resource analysis of Java bytecode

Recent work in resource analysis has translated the idea of amortised resource analysis to imperative languages using a program logic that allows mixing of assertions about heap shapes, in the tradition of separation logic, and assertions about consumable resources. Separately, polyhedral methods have been used to calculate bounds on numbers of iterations in loop-based programs. We are attempting to combine these ideas to deal with Java programs involving both data structures and loops, focusing on the bytecode level rather than on source code

The cost of youth homelessness in Australia study: snapshot report 1

Overview: This is the first national Australian longitudinal study investigating the economic, personal and social costs of youth homelessness over time across a broad range of locations. Too many young Australians are without any form of safe and secure accommodation. It is estimated that approximately 44,000 Australians under the age of 25 are homeless, but the actual number is likely to be higher. Homeless young people comprise some 42 per cent of the Australian homeless population. Participants have been tracked by researchers over a three year period to see what kind of issues young homeless people face: changes in their circumstances, health and quality of life; how many used services; the types of services they accessed; and whether or not they transitioned from homelessness to permanent accommodation

Extending dental nurses' duties: a national survey investigating skill-mix in Scotland's child oral health improvement programme (Childsmile)

Background: Childsmile is Scotland’s national child oral health improvement programme. To support the delivery of prevention in general dental practice in keeping with clinical guidelines, Childsmile sought accreditation for extended duty training for dental nurses to deliver clinical preventive care. This approach has allowed extended duty dental nurses (EDDNs) to take on roles traditionally undertaken by general dental practitioners (GDPs). While skill-mix approaches have been found to work well in general medicine, they have not been formally evaluated in dentistry. Understanding the factors which influence nurses’ ability to fully deliver their extended roles is necessary to ensure nurses’ potential is reached and that children receive preventive care in line with clinical guidance in a cost-effective way. This paper investigates the supplementation of GDPs’ roles by EDDNs, in general dental practice across Scotland. Methods: A cross-sectional postal survey aiming to reach all EDDNs practising in general dental practice in Scotland was undertaken. The survey measured nurses’: role satisfaction, perceived utility of training, frequency, and potential behavioural mediators of, preventive delivery. Frequencies, correlations and multi-variable linear regression were used to analyse the data. Results: Seventy-three percent of practices responded with 174 eligible nurses returning questionnaires. Respondents reported a very high level of role satisfaction and the majority found their training helpful in preparing them for their extended role. While a high level of preventive delivery was reported, fluoride vanish (FV) was delivered less frequently than dietary advice (DA), or oral hygiene advice (OHA). Delivering FV more frequently was associated with higher role satisfaction (p < 0.001). Those nurses who had been practising longer reported delivering FV less frequently than those more recently qualified (p < 0.001). Perceived difficulty of delivering preventive care (skills) and motivation to do so were most strongly associated with frequency of delivery (p < 0.001 for delivery of FV, DA and OHA). Conclusions: This study has provided insight into EDDNs’ experiences and demonstrates that with appropriate training and support, EDDNs can supplement GDPs’ roles in general dental practice in Scotland. However, some barriers to delivery were identified with delivery of FV showing scope for improvement

Molecular and Phenotypic Analysis of Salmonella Biofilm Formation: Exploring the Links Between Survival, Virulence, and Transmission

Pathogenic Salmonella strains are responsible for millions of human and livestock infections each year. The mechanisms of Salmonella pathogenesis are of great interest, along with the capacity of strains to survive in the environment and complete the transmission cycle. This survival is predicted to be related to a specific physiology called a biofilm. Biofilms are communities of cells within a self-produced extracellular matrix that are often associated with a physical surface. For Salmonella, the biofilm phenotype is activated by the transcriptional regulator CsgD and is associated with the production of an extracellular matrix consisting of protein polymers and exopolysaccharides. Salmonella biofilm formation is induced during growth at low temperatures and in conditions of nutrient limitation and low osmolarity. The biofilm phenotype is highly conserved across nontyphoidal Salmonella strains that briefly colonize the host and cause gastroenteritis. It is hypothesized that biofilm formation is important for increasing the transmission success of nontyphoidal Salmonella by enhancing their persistence in non-host environments. Salmonella biofilms have traditionally been studied as a population-level phenotype associated with colony formation, known as the red, dry, and rough (rdar) morphotype. However, Salmonella grown in liquid broth cultures under biofilm-inducing conditions form clonal subpopulations of multicellular aggregates and planktonic cells. This phenomenon is attributed to bistable expression of CsgD, where aggregated cells exist in a CsgD-ON state and planktonic cells are associated with a CsgD-OFF state. We performed comparative transcriptomic sequencing (RNA-seq), which revealed 1856 genes that were differentially expressed between these two S. Typhimurium cell subpopulations. Multicellular aggregates were associated with increased gene expression typical of Salmonella biofilm formation, including nutrient scavenging, reactive oxygen species defenses, and osmoprotection. In contrast, planktonic cells were associated with higher expression of multiple virulence pathways associated with the SPI-1 and SPI-2 type three secretion systems, cell motility, and chemotaxis. Increased synthesis of the SPI-1 type three secretion system in planktonic cells correlated with enhanced invasion of polarized Caco-2 human intestinal cells. We modified an existing Tn7-based transposition system to generate chromosomally marked strains of Salmonella to facilitate tracking of multicellular aggregates and planktonic cells in competitive fitness assays. Planktonic cells were associated with increased virulence in mice compared to multicellular aggregates. However, when these same cell subpopulations were exposed to desiccation, multicellular aggregates were associated with greater cell survival and the virulence advantage of planktonic cells was lost. We hypothesize that bistable CsgD expression and the generation of specialized cell types may represent a form of bet hedging, where planktonic cells are adapted for direct host-to-host transmission, and multicellular aggregates can survive long-term in the environment to cause infections later. This strategy would prepare nontyphoidal Salmonella for the unpredictable nature of the fecal-oral transmission process and improve their potential to cause future infections. Salmonella serovars that cause systemic disease within a restricted range of hosts have been shown to be biofilm-negative. In sub-Saharan Africa, a phylogenetically distinct group of nontyphoidal Salmonella has recently been identified for its role in an emerging epidemic of invasive extraintestinal infections. These invasive nontyphoidal Salmonella are associated with chronic persistence within the human host and do not have an identified environmental reservoir. We compared the biofilm phenotype of two invasive nontyphoidal Salmonella strains (S. Typhimurium D23580 and S. Enteritidis D7795) to a panel of strains consisting of ‘typical’ gastroenteritis-causing, nontyphoidal Salmonella and Salmonella strains that cause systemic typhoid fever. Both strains of invasive nontyphoidal Salmonella demonstrated an impaired biofilm phenotype, which we attributed to strain-specific genetic polymorphisms. We predict that the impaired biofilm phenotype of invasive nontyphoidal Salmonella correlates with their occupation of the systemic niche within the host and a reduced capacity to survive in the environment. My research has brought insight into how pathogenic Salmonella strains are able to navigate through unpredictable areas of their lifecycle and increased our understanding of their potential transmission mechanisms

Elements of person knowledge: Episodic recollection helps us to identify people but not to recognize their faces

Faces automatically draw attention, allowing rapid assessments of personality and likely behaviour. How we respond to people is, however, highly dependent on whether we know who they are. According to face processing models person knowledge comes from an extended neural system that includes structures linked to episodic memory. Here we use scalp recorded brain signals to demonstrate the specific role of episodic memory processes during face processing. In two experiments we recorded Event-Related Potentials (ERPs) while participants made identify, familiar or unknown responses to famous faces. ERPs revealed neural signals previously associated with episodic recollection for identify but not familiar faces. These findings provide novel evidence suggesting that recollection is central to face processing, providing one source of person knowledge that can be used to moderate the initial impressions gleaned from the core neural system that supports face recognition