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The Nature of Phenotypes: Provoking and Measuring the Dynamic Processes of Swarm Expansion, Predation, and Antibiotic Resistance in Myxococcus Xanthus

The question of how genotype affects phenotype has fascinated and puzzled scientists for generations. Regardless of organism, the correlation between observation and underlying condition is necessary for scientists to understand the world around us. Myxococcus xanthus, a fascinating organism with a large genome (7,314 genes), is known for complex social behaviors and is an excellent model system for the study of this relationship. Upon starvation, M. xanthus cells condense into large multicellular aggregates to await renewed nutrient availability. M. xanthus cells swarm together on surfaces as a predatory biofilm, lysing and killing prey as a singular unit. During predation, swarms display dynamic multicellular patterns called ripples. Individual cells also retain the ability to move independently, leaving behind a slime trail for other cells to follow. This creates complex flare structures at the edge of multicellular swarms. The first part of this thesis addresses the problem of genotype-to-phenotype accuracy in complex organisms. Using 50 single gene knockout M. xanthus strains, I performed the traditional motility phenotype assay as well as a novel motility phenotype assay under magnification. Comparison of these results demonstrates not only that genes not related to motility machinery can induce a motility phenotype, but also that motility phenotypes are dynamic and can change over time. Additionally, I demonstrate that motility phenotype can change significantly when swarms move over prey, as opposed to simple agar surfaces. This more in-depth analysis allows for phenotypic classification of knockout strains previously thought to be without phenotype. The complexity of the M. xanthus genome is not only responsible for its incredibly complex multicellular phenotype, but for its potential use as a model for the study of antibiotic resistance and production of novel antibiotic compounds. The production of secondary metabolites like antibiotics is not ubiquitous in bacteria. The unique resources or building blocks required for their manufacture as well as their complicated molecular scaffolds restricts their production to more complex organisms like M. xanthus. The laboratory-friendly and non-pathogenic nature of M. xanthus adds another category to its list of interesting attributes. By sharing many qualities with pathogenic bacteria while remaining a biosafety level one organism, M. xanthus represents a unique opportunity to study how antibiotic resistance is obtained, maintained, and compensated for in a complex genome. The second part of this thesis studies M. xanthus\u27 usefulness in the fight against antibiotic resistance. I created strains of M. xanthus resistant to a wide variety of antibiotics. Some were exposed to initially low concentrations slowly building over time while others experienced higher antibiotic concentrations over a shorter period. The creation of these strains, simulating the manner in which pathogenic bacteria may gain resistance to antibiotics in vivo, allowed for a laboratory-friendly study of phenotypes and fitness costs associated with varying levels of resistance. I also supply preliminary proof of antibiotic-resistant M. xanthus\u27 utility as a general heterologous host for novel antibiotics. Upon introduction of the oxytetracycline gene cluster, resistant strains were significantly more likely to retain the plasmid than WT. These results represent an important step in both understanding how and why antibiotic resistance arises in complex bacteria as well as a potential mechanism for novel antibiotic discovery

The search for a coherent and universal feminist theory of international relations : a critical assessment

[From the introduction];This thesis has three interlocking aims. The first is to examine the extension in recent decades of feminist theory to International Relations. The second is to consider the challenge of some leading non-Western feminist thinkers to key assumptions about International Relations made by Western thinkers. The third objective is to consider the implications of feminist theory for political practice. This is achieved through an examination of the recent attempt by the United States to implement a female emancipation project based on Western universal values, in Afghanistan

Patient and public attitudes to and awareness of clinical practice guidelines : a systematic review with thematic and narrative syntheses

Article Accepted Date: 15 July 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 258583 (DECIDE project). The Health Services Research Unit, Aberdeen University, is funded by the Chief Scientist Office of the Scottish Government Health Directorates. The authors accept full responsibility for this paper and the views expressed in it are those of the authors and do not necessarily reflect those of the Chief Scientist Office. NS receives funding through a Knowledge Translation Fellowship from the Canadian Institutes of Health Research. No funding bodies had a role in the manuscript. We would like to thank Healthcare Improvement Scotland and the University of Dundee for support, including access to literature. We would also like to thank Lorna Thompson (Healthcare Improvement Scotland), for her help with the protocol for this review.Peer reviewedPublisher PD

Improving The Effectiveness Of Human Resources Practices Through Transforming Care At The Bedside

In 2010, in an effort to increase patient involvement in decision-making about health care redesign, a Quebec university health care organization implemented the Transforming Care at the Bedside (TCAB). This article presents the results from a qualitative study exploring health professionals’ perceptions of TCAB and the effect on turnover and overtime. This descriptive, qualitative study utilized focus groups, individual interviews, and a review of administrative documents for data collection. Participants included hospital workers from five units implementing TCAB. The data generated by the interviews and focus groups were analyzed using NVivo with the method proposed by Miles and Huberman (1994). During the first year of implementation of TCAB, the team noted the importance of taking time to see the effects of the changes and thereby facilitate the involvement of other team members. A number of TCAB team members also cited communication as a facilitating element for informing team members of changes. According to the participants, the TCAB strategies that were implemented have had a positive impact on practice and on the work environment, and turnover showed an improvement. There was no change in absenteeism. TCAB has the potential to impact not only nurses’ work, but interprofessional team work as well, through changes that involve everyone. Future research should focus on how to support team members to reduce resistance to change and increase social support in order to implement and sustain changes.

GK Housing First - UWE Evaluation Report FINAL Retraction 29-10-2021

Housing First is an evidence-based approach which supports people with multiple complex needs and entrenched homelessness to live in their own homes. Funded by Bristol City Council in 2018, Golden Key initiated a Housing First pilot to establish the feasibility of delivering high fidelity Housing First in the local Bristol context of extreme affordable housing shortages. This has since expanded over three phases to house and support 28 people of the 40 recruited who have the highest and most entrenched multiple complex needs (all data contained in this report up to December 2020).The Golden Key Local Evaluation Team at UWE developed an evaluation framework collaboratively with Golden Key and designed evaluation activity aligned with this framework. The evaluation research activity included two rounds of semi-structured stakeholder interviews, (May 2018 and Dec 2020-Jan 2021), quantitative analysis of clients’ demographic, engagement, and outcome assessment data (taken at the end of 2020), and a client journey mapping exercise. The journey mapping was unfortunately limited due to the pandemic which has severely restricted the evaluation’s ability to understand the client’s experience

Integrating the digital and the traditional to deliver therapy for depression:lessons from a pragmatic study

Traditional approaches to psychotherapy emphasise face-to-face contact between patients and therapists. In contrast, current computerised approaches tend to minimise this contact. This can limit the range of mental health difficulties for which computerised approaches are effective. Here, we explore an alternative approach that integrates face-to-face contact, electronic contact, online collaboration, and support for between-session activities. Our discussion is grounded in the design of a platform to deliver psychotherapy for depression. We report findings of an 11-month pragmatic study in which 17 patients received treatment for depression via the platform. Results show how design decisions had a significant impact on the dynamics of therapeutic sessions and the establishment of patient-therapist relationships. For example, the use of instant messaging for synchronous, in-session contact slowed communication, but also provided a valuable space for reflection and helped to maintain session focus. We discuss the impact of flexibility and the potential of integrated approaches to both enhance and reduce patient engagement

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people