Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.

Project Sanitarium: gaming TB: a serious game for a serious problem

Collaborative projects between Industry and Academia provide excellent opportunities for learning. Throughout the academic year 2014-2015 undergraduates from the School of Arts, Media and Computer Games at Abertay University worked with academics from the Infection Group at the University of St Andrews and industry partners Microsoft and DeltaDNA. The result was a serious game prototype that utilized game design techniques and technology to demystify and educate players about the diagnosis and treatment of one of the world's oldest and deadliest diseases, Tuberculosis (TB). Project Sanitarium is a game incorporating a mathematical model that is based on data from real-world drug trials. This paper discusses the project design and development, demonstrating how the project builds on the successful collaborative pedagogical model developed by academic staff at Abertay University. The aim of the model is to provide undergraduates with workplace simulation, wider industry collaboration and access to academic expertise to solve challenging and complex problems.

Accommodating interruptions: a grounded theory of young people with asthma

Background: Accommodating Interruptions is a theory that emerged in the context of young people who have asthma. A background to the prevalence and management of asthma in Ireland is given to situate the theory. Ireland has the fourth highest incidence of asthma in the world, with almost one in five Irish young people having asthma. Although national and international asthma management guidelines exist it is accepted that the symptom control of asthma among the young people population is poor. Aim: The aim of this research is to investigate the lives of young people who have asthma, to allow for a deeper understanding of the issues affecting them. Methods: This research was undertaken using a Classic Grounded Theory approach. It is a systematic approach to allowing conceptual emergence from data in generating a theory that explains behaviour in resolving the participant’s main concern. The data were collected through in-depth interviews with young people aged 11-16 years who had asthma for over one year. Data were also collected from participant diaries. Constant comparative analysis, theoretical coding and memo writing were used to develop the theory. Results: The theory explains how young people resolve their main concern of being restricted, by maximizing their participation and inclusion in activities, events and relationships in spite of their asthma. They achieve this by accommodating interruptions in their lives in minimizing the effects of asthma on their everyday lives. Conclusion: The theory of accommodating interruptions explains young people’s asthma management behaviours in a new way. It allows us to understand how and why young people behave the way they do in order minimise the effect of asthma on their lives. The theory adds to the body of knowledge on young people with asthma and challenges some viewpoints regarding their behaviours.

Anticipatory vigilance: A classic grounded theory of risk reduction and management in the perioperative setting

This research aimed to investigate the main concern facing nurses in minimising risk within the perioperative setting and to generate an explanatory substantive theory of how they resolve this through anticipatory vigilance. In the context of the perioperative setting, nurses encounter challenges in minimising risks for their patients on a continuous basis. Current explanations of minimising risk in the perioperative setting offers insights into how perioperative nurses undertake their work. Currently research in minimising risk is broadly related to dealing with errors as opposed to preventing them. To date, little is known about how perioperative nurses practice and maintain safety. This study was guided by the principles of classic grounded theory as described by Glaser (1978, 1998, 2001). Data was collected through individual unstructured interviews with thirty seven perioperative nurses (with varying lengths of experiences of working in the area) and thirty three hours of non-participant observation within eight different perioperative settings in the Republic of Ireland. Data was simultaneously collected and analysed. The theory of anticipatory vigilance emerged as the pattern of behaviour through which nurse’s deal with their main concern of minimising risk in a high risk setting. Anticipatory vigilance is enacted through orchestrating, routinising and momentary adapting within a spirit of trusting relations within the substantive area of the perioperative setting. This theory of offers an explanation on how nurses resolve their main concern of minimising risk within the perioperative setting. The theory of anticipatory vigilance will be useful to nurses in providing a comprehensive framework of explanation and understanding on how nurses deal with minimising risk in the perioperative setting. The theory links perioperative nursing, risk and vigilance together. Clinical improvements through understanding and awareness of the theory of anticipatory vigilance will result in an improved quality environment, leading to safe patient outcomes.

Moral shielding: A grounded theory of integrity maintenance in multidisciplinary teams

Using a classic grounded theory methodology (CGT), this study explores the phenomenon of moral shielding within mental health multidisciplinary teams (MDTS). The study was located within three catchment areas engaged in acute mental health service practice. The main concern identified was the maintenance of a sense of personal integrity during situational binds. Through theoretical sampling thirty two practitioners, including; doctors, nurses, social workers, occupational therapists, counsellors and psychologists, where interviewed face to face. In addition, emergent concepts were identified through observation of MDTs in clinical and research practice. Following a classic grounded theory methodology, data collection and analysis occurred simultaneously. A constant comparative approach was adopted and resulted in the immergence of three sub- core categories; moral abdication, moral hinting and pseudo-compliance. Moral abdication seeks to re-position within an event in order to avoid or deflect the initial obligation to act, it is a strategy used to remove or reduce moral ownership. Moral gauging represents the monitoring of an event with the goal of judging the congruence of personal principles and commitments with that of other practitioners. This strategy is enacted in a bid to seek allies for the support of a given moral position. Pseudo-compliance represents behaviour that hides desired principles and commitments in order to shield them from challenge. This strategy portrays agreement with the dominant position within the MDT, whilst holding a contrary position. It seeks to preserve a reservoir of emotional energy required to maintain a sense of personal integrity. Practitioners who were successful in enacting moral shielding were found to not experience significant emotional distress associated with the phenomenon of moral distress; suggesting that these practitioners had found mechanisms to manage situational binds that threatened their sense of personal integrity.

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice.

Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders.

Implementation of customer relationship management and inventory control software: a multiple case study of small retailers

Gemstone Team Small Business Solutions

Specialist and primary care physicians' views on barriers to adequate preparation of patients for renal replacement therapy: a qualitative study.

BACKGROUND: Early preparation for renal replacement therapy (RRT) is recommended for patients with advanced chronic kidney disease (CKD), yet many patients initiate RRT urgently and/or are inadequately prepared. METHODS: We conducted audio-recorded, qualitative, directed telephone interviews of nephrology health care providers (n = 10, nephrologists, physician assistants, and nurses) and primary care physicians (PCPs, n = 4) to identify modifiable challenges to optimal RRT preparation to inform future interventions. We recruited providers from public safety-net hospital-based and community-based nephrology and primary care practices. We asked providers open-ended questions to assess their perceived challenges and their views on the role of PCPs and nephrologist-PCP collaboration in patients' RRT preparation. Two independent and trained abstractors coded transcribed audio-recorded interviews and identified major themes. RESULTS: Nephrology providers identified several factors contributing to patients' suboptimal RRT preparation, including health system resources (e.g., limited time for preparation, referral process delays, and poorly integrated nephrology and primary care), provider skills (e.g., their difficulty explaining CKD to patients), and patient attitudes and cultural differences (e.g., their poor understanding and acceptance of their CKD and its treatment options, their low perceived urgency for RRT preparation; their negative perceptions about RRT, lack of trust, or language differences). PCPs desired more involvement in preparation to ensure RRT transitions could be as "smooth as possible", including providing patients with emotional support, helping patients weigh RRT options, and affirming nephrologist recommendations. Both nephrology providers and PCPs desired improved collaboration, including better information exchange and delineation of roles during the RRT preparation process. CONCLUSIONS: Nephrology and primary care providers identified health system resources, provider skills, and patient attitudes and cultural differences as challenges to patients' optimal RRT preparation. Interventions to improve these factors may improve patients' preparation and initiation of optimal RRTs.

Proyecto "mete" (mathematics education traditions of europe): el foco matemático

Este artículo presenta los resultados de un estudio sobre las tradiciones de enseñanza en cuatro países europeos: Bélgica (Flandes), Inglaterra, Hungría y España. Se trata de un estudio a pequeña escala en el que se emplean métodos cuantitativos y cualitativos, y que, en lugar de pretender obtener generalizaciones, está orientado a arrojar alguna luz que posibilite la mejora de la enseñanza y el aprendizaje de las matemáticas. Establece comparaciones con los resultados de los test TIMSS y PISA y extrae alguna conclusión para la formación inicial de maestros y profesores de matemáticas. Extraemos de éste los resultados relativos a los datos cuantitativos y nos centramos en el foco matemático.

Integrating personnel movement simulation into preliminary ship design

Traditionally, when designing a ship the driving issues are seen to be powering, stability, strength and seakeeping. Issues related to ship operations and evolutions are investigated later in the design process, within the constraint of a fixed layout. This can result in operational inefficiencies and limitations, excessive crew numbers and potentially hazardous situations. University College London and the University of Greenwich are in the final year of a three year EPSRC funded research project to integrate the simulation of personnel movement into early stage ship design. This allows the assessment of onboard operations while the design is still amenable to change. The project brings together the University of Greenwich developed maritimeEXODUS personnel movement simulation software and the SURFCON implementation of the Design Building Block approach to early stage ship design, which originated with the UCL Ship Design Research team. Central to the success of this project is the definition of a suitable series of Naval Combatant Human Performance Metrics which can be used to assess the performance of the design in different operational scenarios. The paper outlines the progress made on deriving the human performance metric from human factors criteria measured in simulations and their incorporation into a Behavioural Matrix for analysis. It describes the production of a series of SURFCON ship designs based on the RN Type 22 Batch 3 frigate, and their analysis using the PARAMARINE and maritimeEXODUS software. Conclusions to date will be presented on the integration of personnel movement simulation into the preliminary ship design process.

Integrating personnel movement simulation into prelimary ship design

Traditionally, when designing a ship the driving issues are seen to be powering, stability, strength and seakeeping. Issues related to ship operations and evolutions are investigated later in the design process, within the constraint of a fixed layout. This can result in operational inefficiencies and limitations, excessive crew numbers and potentially hazardous situations. This paper summarises work by University College London and the University of Greenwich prior to the completion of a three year EPSRC funded research project to integrate the simulation of personnel movement into early stage ship design. This integration is intended to facilitate the assessment of onboard operations while the design is still highly amenable to change. The project brings together the University of Greenwich developed maritimeEXODUS personnel movement simulation software and the SURFCON implementation of the Design Building Block approach to early stage ship design, which originated with the UCL Ship Design Research team and has been implemented within the PARAMARINE ship design system produced by Graphics Research Corporation. Central to the success of this project is the definition of a suitable series of Performance Measures (PM) which can be used to assess the human performance of the design in different operational scenarios. The paper outlines the progress made on deriving the PM from human dynamics criteria measured in simulations and their incorporation into a Human Performance Metric (HPM) for analysis. It describes the production of a series of SURFCON ship designs, based on the Royal Navy’s Type 22 Batch 3 frigate, and their analysis using the PARAMARINE and maritimeEXODUS software. Conclusions on the work to date and for the remainder of the project are presented addressing the integration of personnel movement simulation into the preliminary ship design process.

Coastal Zone Ecosystem Services: From science to values and decision making; a case study

This research is concerned with the following environmental research questions: socio-ecological system complexity, especially when valuing ecosystem services; ecosystems stock and services flow sustainability and valuation; the incorporation of scale issues when valuing ecosystem services; and the integration of knowledge from diverse disciplines for governance and decision making. In this case study, we focused on ecosystem services that can be jointly supplied but independently valued in economic terms: healthy climate (via carbon sequestration and storage), food (via fisheries production in nursery grounds), and nature recreation (nature watching and enjoyment). We also explored the issue of ecosystem stock and services flow, and we provide recommendations on how to value stock and flows of ecosystem services via accounting and economic values respectively. We considered broadly comparable estuarine systems located on the English North Sea coast: the Blackwater estuary and the Humber estuary. In the past, these two estuaries have undergone major land-claim. Managed realignment is a policy through which previously claimed intertidal habitats are recreated allowing the enhancement of the ecosystem services provided by saltmarshes. In this context, we investigated ecosystem service values, through biophysical estimates and welfare value estimates. Using an optimistic (extended conservation of coastal ecosystems) and a pessimistic (loss of coastal ecosystems because of, for example, European policy reversal) scenario, we find that context dependency, and hence value transfer possibilities, vary among ecosystem services and benefits. As a result, careful consideration in the use and application of value transfer, both in biophysical estimates and welfare value estimates, is advocated to supply reliable information for policy making.