Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

The effectiveness of workplace coaching:A meta-analysis of learning and performance outcomes; scale development; theoretical model of individual differences and longitudinal study

The extant literature on workplace coaching is characterised by a lack of theoretical and empirical understanding regarding the effectiveness of coaching as a learning and development tool; the types of outcomes one can expect from coaching; the tools that can be used to measure coaching outcomes; the underlying processes that explain why and how coaching works and the factors that may impact on coaching effectiveness. This thesis sought to address these substantial gaps in the literature with three linked studies. Firstly, a meta-analysis of workplace coaching effectiveness (k = 17), synthesizing the existing research was presented. A framework of coaching outcomes was developed and utilised to code the studies. Analysis indicated that coaching had positive effects on all outcomes. Next, the framework of outcomes was utilised as the deductive start-point to the development of the scale measuring perceived coaching effectiveness. Utilising a multi-stage approach (n = 201), the analysis indicated that perceived coaching effectiveness may be organised into a six factor structure: career clarity; team performance; work well-being; performance; planning and organizing and personal effectiveness and adaptability. The final study was a longitudinal field experiment to test a theoretical model of individual differences and coaching effectiveness developed in this thesis. An organizational sample of 84 employees each participated in a coaching intervention, completed self-report surveys, and had their job performance rated by peers, direct reports and supervisors (a total of 352 employees provided data on participant performance). The results demonstrate that compared to a control group, the coaching intervention generated a number of positive outcomes. The analysis indicated that coachees’ enthusiasm, intellect and orderliness influenced the impact of coaching on outcomes. Mediation analysis suggested that mastery goal orientation, performance goal orientation and approach motivation in the form of behavioural activation system (BAS) drive, were significant mediators between personality and outcomes. Overall, the findings of this thesis make an original contribution to the understanding of the types of outcomes that can be expected from coaching, and the magnitude of impact coaching has on outcomes. The thesis also provides a tool for reliably measuring coaching effectiveness and a theoretical model to understand the influence of coachee individual differences on coaching outcomes.

Public attitudes on the ethics of deceptively planting false memories to motivate healthy behavior

Researchers have proposed that planting false memories could have positive behavioral consequences. The idea of deceptively planting “beneficial” false memories outside of the laboratory raises important ethical questions, but how might the general public appraise this moral dilemma? In two studies, participants from the USA and UK read about a fictional “false-memory therapy” that led people to adopt healthy behaviors. Participants then reported their attitudes toward the acceptability of this therapy, via scale-rating (both studies) and open-text (Study 2) responses. The data revealed highly divergent responses to this contentious issue, ranging from abject horror to unqualified enthusiasm. Moreover, the responses shed light on conditions that participants believed would make the therapy less or more ethical. Whether or not deceptively planting memories outside the lab could ever be justifiable, these studies add valuable evidence to scientific and societal debates on neuroethics, whose relevance to memory science is increasingly acute.

The effects of using an alternative method for teaching badminton to post secondary level students in Taiwan

The effect of teaching method in physical education is an important issue and has been a concern of the expert teacher. Teachers are expected to create a model of teaching in their field; therefore, it is reasonable to question what is the effect of an alternative teaching method on student performance in physical education. This study explores whether teaching methods with advanced planning, behavior and belief in high enthusiasm, use of instructional strategies and evaluation, together termed a systematic teaching approach, used in a physical education activity would provide an effective environment for learning which supports student achievement in the psychomotor, cognitive, and affective domains. This study also investigated whether there was a difference in performance between students who were taught with a systematic teaching approach and students who were taught with the traditional teaching model. Information was collected using two performance skills, a written test, and one questionnaire. The 68 participants were randomly assigned into either an experimental group or a control group. Two teachers were assigned to either the experimental group or the control group. The teaching experiment took place at Tamsui Oxford University College in Taiwan and lasted eight weeks. ^ Research questions were analyzed using the t-test. Results indicated that a significant difference in students' performance was found between the experimental group and the control group on both the skill tests and the paper test. Analysis of student attitude toward their teacher and their course on the questionnaire indicated a significant difference between the experimental group and the control group. ^ The findings of this study imply that students who were taught with a systematic teaching style were significantly superior to students who were taught with the traditional model on these measures. This finding supports the contention that effective teaching in physical education is related to advanced planning, high enthusiasm, instructional strategy and evaluation and that all physical education teachers should implement these planning elements in the development of the teaching strategies. ^

Readiness for school: A study of parent, teacher, and preschool provider perspectives

A possible gap exists between what parents and preschool providers know concerning children's readiness for school and what they should know when compared to teacher expectations. Students are experiencing difficulty in early schooling as a result of this gap in perspectives. This study's purpose was to describe, explain, and analyze the perspectives of parents, teachers, and preschool providers concerning school readiness. The qualitative strategy of interviewing was used with six parents, six teachers, and two preschool provider participants. Interview transcripts, field notes, member checking, and document analysis were used to interpret data and support findings. Categorization and coding organized data and aided in theory development. ^ Major findings of the study include: (a) All participant groups stress social skills, communication skills, and enthusiasm as most valuable for school readiness; (b) All participant groups agree parents have primary responsibility for readiness preparation; (c) Many participants suggest variables concerning family, economics, and home life contribute to a lack of readiness; (d) Parents place greater value on academic skills than teachers or preschool providers; (e) Preschool programs are identified as having the potential to significantly influence readiness; (f) Communicating, providing positive learning experiences, and providing preschool experience are valuable ways to prepare students for school, yet, differences were found in the types of experiences noted; (g) Participant perspectives indicate that informing parents of readiness expectations is of major importance, and they offer suggestions to accomplish this goal such as using public libraries and pediatrician offices as houses for written information and having kindergarten teachers make presentations at preschools. ^ This study concludes that parents and preschool providers do have knowledge concerning readiness for school. They may not, however, be in a position to carry out their responsibilities due to the intervening variables that inhibit the amount of time, interaction, and communication they have with the children in their care. This study discloses the beliefs of parents and preschool providers that children are ready for school, while teachers conclude that many children are not ready. Suggestions for readiness preparation and information dissemination are significant findings that offer implications for practice and future study. ^

Gnosticism, Transformation, and the Role of the Feminine in the Gnostic Mass of the Ecclesia Gnostica Catholica (E.G.C.)

The Gnostic Mass of the Ecclesia Gnostica Catholica (E.G.C.) suggests a heterosexual gender binary in which the female Priestess seated on the altar as the sexual and fertile image of the divine feminine is directed by the male Priest’s activity, desire and speech. The apparent contradiction between the empowered individual and the polarized gender role was examined by comparing the ritual symbolism of the feminine with the interpretations of four Priestesses and three Priests (three pairs plus one). Findings suggest that the Priestess’ role in the Gnostic Mass is associated with channeling, receptivity, womb, cup, and fertility, while the Priest’s role is associated with enthusiasm, activity, phallus, lance, and virility. Despite this strong gender duality, the Priestesses asserted that their role was personally and spiritually empowering, and they maintained heterosexual and polarized gendered roles are necessary in a transformative ritual which ultimately reveals the godlike unified individual.

Utilização de mapas conceituais como ferramenta de ensino para o desenvolvimento do raciocínio clínico no curso de medicina da Universidade Federal do Rio Grande do Norte

BACKGROUND: Among the wide range of skills displayed by a medical doctor is undoubtedly the need to use cohesive and well grounded clinical reasoning in order for medical care to be indeed effective. It is in this respect that conceptual maps emerge; these are a methodological innovation that allows a comprehensive, panoramic and associative outlook of theoretical content, making it more practical and applicable to the reality of clinical observation. Promoting learning, learning resources and a feedback system between professor and students, as well as assessing and monitoring the performance of students during their academic training, are the main features of this tool. OBJETIVE: Assess the use of conceptual maps as a teaching-learning tool in the training of undergraduate medical students at Universidade Federal do Rio Grande do Norte (UFRN). METHODOLOGY: Interventional, randomized, cross-sectional study conducted with students from the 3rd and 5th periods of the medical course at UFRN, during the second semester of 2014, totaling 86 participants, divided into two groups: GI (intervention – clinical case resolution with a conceptual map) and GII (control – clinical case resolution without a conceptual map) in each period. RESULTS: The use of conceptual maps to teach liver failure syndrome resulted in a statistically significant cognitive gain for G1 students from the 5th period (GI: 6.8±1.6 and 8.0±1.5, p = 0.024; GII: 7.2±2.1 and 8.0±1.7, p = 0.125, pre and post-intermediate means, respectively), a result not observed in the period 3rd (GI: 7.7±1.3 and 8.0±1.4, p = 0.501; GII: 6.7±1.8 and 7.8±1.8; p=0.068, pre and post-intermediate means, respectively). Students in the 3 rd period gave better responses to the first clinical case, with a larger number of suitable concepts and crosslinks, when they used conceptual maps (GI: 91.3±13.15 and GII: 64.84±22.84, p=0,002). Students in the 5th period exhibited better clinical reasoning and more complete responses using the tool (p=0,01). Most of the students were not aware of the tool (53.8% from the 3rd period and 65.3% from the 5th period). Among those who knew about conceptual maps, most (59.3%) had only used them during high school, 14.8% had never used them and only seven students (25.9%) used them during the medical course. Analysis of open responses, obtained in process assessment showed clear satisfaction and enthusiasm with learning about the new tool, and frequent suggestions to use it at other moments in the course. Assessment of learning profile, using the VARK questionnaire, showed that most students from both periods exhibited a multimodal style. CONCLUSION: Despite their scant knowledge regarding the tool, good acceptability and understanding was observed in the study participants. The conceptual maps allowed cognitive gains, better responses and clinical reasoning in teaching liver failure syndrome to 5th period students.

The Bennachie Colony : A Nineteenth-Century Informal Community in Northeast Scotland

Acknowledgments The investigation of the Bennachie Colony is part of a broader initiative called the Bennachie Landscape Project, a collaborative endeavour between the Bailies of Bennachie and the University of Aberdeen. To date, funding for the project has been generously provided by the Arts and Humanities Research Council (AHRC) in the form of a Connected Communities Grant (G. Noble PI) and more recently through a larger Development Grant (J. Oliver PI). The research that this paper is based on could not have been undertaken without the generous assistance of a large number of volunteers, university students and staff members. While it would be impossible to name everyone who has contributed, we would like to acknowledge the regular members of the “landscape group” whose infective enthusiasm for the project has provided a stimulating environment for learning and co-production. Particular thanks go to Jackie Cumberbirch, Barry Foster, Chris Foster, Angela Groat, David Irving, Alison Kennedy, Harry Leal, Ken Ledingham, Colin Miller, Iain Ralston, Colin Shepherd, Sue Taylor and Andrew Wainwright. Further assistance with fieldwork was provided by Ágústa Edwald, Patrycia Kupiec, Barbora Wouters, Óskar Sveinbjarnarson, members of Northlight Heritage and several cohorts worth of University of Aberdeen undergraduate and graduate students. We are indebted to the RCAHMS for assistance with plane table survey and to Óskar Sveinbjarnarson for help with mapping. Others have supported additional aspects of the Bennachie Landscape project or have provided specialist advice. Thanks go to Neil Curtis, Liz Curtis, Rowan Ellis, Marjory Harper, Siobhan Convery and the University of Aberdeen Special Collections staff. Access to undertake fieldwork was graciously provided by the Forestry Commission Scotland. Helpful comments on earlier drafts of this paper were provided by Barry and Chris Foster, Ken Ledingham, Collin Miller, Collin Shepherd, Sue Taylor, Andrew Wainwright and two anonymous reviewers.

The Bennachie Colony : A Nineteenth-Century Informal Community in Northeast Scotland

Acknowledgments The investigation of the Bennachie Colony is part of a broader initiative called the Bennachie Landscape Project, a collaborative endeavour between the Bailies of Bennachie and the University of Aberdeen. To date, funding for the project has been generously provided by the Arts and Humanities Research Council (AHRC) in the form of a Connected Communities Grant (G. Noble PI) and more recently through a larger Development Grant (J. Oliver PI). The research that this paper is based on could not have been undertaken without the generous assistance of a large number of volunteers, university students and staff members. While it would be impossible to name everyone who has contributed, we would like to acknowledge the regular members of the “landscape group” whose infective enthusiasm for the project has provided a stimulating environment for learning and co-production. Particular thanks go to Jackie Cumberbirch, Barry Foster, Chris Foster, Angela Groat, David Irving, Alison Kennedy, Harry Leal, Ken Ledingham, Colin Miller, Iain Ralston, Colin Shepherd, Sue Taylor and Andrew Wainwright. Further assistance with fieldwork was provided by Ágústa Edwald, Patrycia Kupiec, Barbora Wouters, Óskar Sveinbjarnarson, members of Northlight Heritage and several cohorts worth of University of Aberdeen undergraduate and graduate students. We are indebted to the RCAHMS for assistance with plane table survey and to Óskar Sveinbjarnarson for help with mapping. Others have supported additional aspects of the Bennachie Landscape project or have provided specialist advice. Thanks go to Neil Curtis, Liz Curtis, Rowan Ellis, Marjory Harper, Siobhan Convery and the University of Aberdeen Special Collections staff. Access to undertake fieldwork was graciously provided by the Forestry Commission Scotland. Helpful comments on earlier drafts of this paper were provided by Barry and Chris Foster, Ken Ledingham, Collin Miller, Collin Shepherd, Sue Taylor, Andrew Wainwright and two anonymous reviewers.

A theory-informed approach to developing visually mediated interventions to change behaviour using an asthma and physical activity intervention exemplar

Funding for this study was received from the Chief Scientist Office for Scotland. We would like to thank Asthma UK and Asthma UK Scotland for facilitating the advertisement of the study pilot and consultative user group. Thanks to Dr Mark Grindle for his helpful discussions concerning narrative. Thanks also to Mr Mark Haldane who designed the characters, backgrounds, and user interface used within the 3D computer animation. Particular thanks to the participants of the consultative user group for their enthusiasm, comments, and suggestions at all stages of the intervention design.

La enseñanza oficial de cine en España

En este artículo se recoge la historia de la enseñanza oficial de cine en España: los dos centros en los que se llevó a cabo, sus sedes, sus directores y las prácticas de fin de carrera. Todo ello visto desde la división en tres etapas del tiempo de existencia de la enseñanza anterior a su incorporación a la universidad: la etapa fundacional, la edad de oro y la crisis que lleva al cierre. A lo largo de estas tres etapas hubo un cambio de actitud en el alumnado, desde el entusiasmo y la ilusión inicial al desencanto y rechazo absoluto hacia la Escuela en los últimos años. 

Designing an interactive laboratory experiment to investigate buoyancy

Laboratory classes provide a visual and practical way of supplementing traditional teaching through lectures and tutorial classes. A criticism of laboratories in our School is that they are largely based on demonstration with insufficient participation by students. This provided the motivation to create a new laboratory experiment which would be interactive, encourage student enthusiasm with the subject and improve the quality of student learning.

The topic of the laboratory is buoyancy. While this is a key topic in the first-year fluids module, the laboratory has been designed in such a way that prior knowledge of the topic is unnecessary and therefore it would be accessible by secondary school pupils. The laboratory climaxes in a design challenge. However, it begins with a simple task involving students identifying some theoretical background information using given websites. They then have to apply their knowledge by developing some equations. Next, given some materials (a sheet of tinfoil, card and blu-tack), they have to design a vessel to carry the greatest mass without sinking. Thus, they are given an open-ended problem and have to provide a mathematical justification for their design. Students are expected to declare the maximum mass for their boat in advance of it being tested to create a sense of competition and fun. Overall, the laboratory involves tasks which begin at a low level and progressively get harder, incorporating understanding, applying, evaluating and designing (with reference to Bloom’s taxonomy).

The experiment has been tested in a modern laboratory with wall-mounted screens and access to the internet. Students enjoyed the hands-on aspect and thought the format helped their learning.

The use of cheap materials which are readily available means that many students can be involved at one time. Support documentation has been produced, both for the student participants and the facilitator. The latter is given advice on how to guide the students (without simply giving them the answer) and given some warning about potential problems the students might have.

The authors believe that the laboratory can be adapted for use by secondary school pupils and hope that it will be used to promote engineering in an engaging and enthusing way to a wider audience. To this end, contact has already been made with the Widening Participation Unit at the University to gain advice on possible next steps.

GPs’ and community pharmacists’ opinions on medication management at transitions of care in Ireland

Objective. The aim of this study was to survey GPs and community pharmacists (CPs) in Ireland regarding current practices of medication management, specifically medication reconciliation, communication between health care providers and medication errors as patients transition in care.
Methods. A national cross-sectional survey was distributed electronically to 2364 GPs, 311 GP Registrars and 2382 CPs. Multivariable associations comparing GPs to CPs were generated and content analysis of free text responses was undertaken.
Results. There was an overall response rate of 17.7% (897 respondents—554 GPs/Registrars and 343 CPs). More than 90% of GPs and CPs were positive about the effects of medication reconciliation on medication safety and adherence. Sixty per cent of GPs reported having no formal system of medication reconciliation. Communication between GPs and CPs was identified as good/very good by >90% of GPs and CPs. The majority (>80%) of both groups could clearly recall prescribing errors, following a transition of care, they had witnessed in the previous 6 months. Free text content analysis corroborated the positive relationship between GPs and CPs, a frustration with secondary care communication, with many examples given of prescribing errors.
Conclusions. While there is enthusiasm for the benefits of medication reconciliation there are limited formal structures in primary care to support it. Challenges in relation to systems that support inter-professional communication and reduce medication errors are features of the primary/secondary care transition. There is a need for an improved medication management system. Future research should focus on the identified barriers in implementing medication reconciliation and systems that can improve it.

Using protocols in ICU practice. Engaging the staff.

Aims/Purpose: Protocols are evidenced-based structured guides for directing care to achieve improvements. But translating that evidence into practice is a major challenge. It is not acceptable to simply introduce the protocol and expect it to be adopted and lead to change in practice. Implementation requires effective leadership and management. This presentation describes a strategy for implementation that should promote successful adoption and lead to practice change.
Presentation description: There are many social and behavioural change models to assist and guide practice change. Choosing a model to guide implementation is important for providing a framework for action. The change process requires careful thought, from the protocol itself to the policies and politics within the ICU. In this presentation, I discuss a useful pragmatic guide called the 6SQUID (6 Steps in QUality Intervention Development). This was initially designed for public health interventions, but the model has wider applicability and has similarities with other change process models. Steps requiring consideration include examining the purpose and the need for change; the staff that will be affected and the impact on their workload; and the evidence base supporting the protocol. Subsequent steps in the process that the ICU manager should consider are the change mechanism (widespread multi-disciplinary consultation; adapting the protocol to the local ICU); and identifying how to deliver the change mechanism (educational workshops and preparing staff for the changes are imperative). Recognising the barriers to implementation and change and addressing these locally is also important. Once the protocol has been implemented, there is generally a learning curve before it becomes embedded in practice. Audit and feedback on adherence are useful strategies to monitor and sustain the changes.
Conclusion: Managing change successfully will promote a positive experience for staff. In turn, this will encourage a culture of enthusiasm for translating evidence into practice.

Developing Innovative TEL Practice in Teacher Education

This interactive symposium will focus on the use of different technologies in developing innovative practice in teacher education at one university in England. Technology Enhanced Learning (TEL) is a field of educational policy and practice that has the power to ignite diametrically opposing views and reactions amongst teachers and teacher educators, ranging across a spectrum from immense enthusiasm to untold terror. In a field where the skills and experience of individuals vary from those of digital natives (Prensky 2001) to lags and lurkers in digital spaces, the challenges of harnessing the potential of TEL are complex. The challenges include developing the IT skills of trainees and educators and the creative application of these skills to pedagogy in all areas of the curriculum. The symposium draws on examples from primary, secondary and post-compulsory teacher education to discuss issues and approaches to developing research capacity and innovative practice using different etools, many of which are freely available. The first paper offers theoretical and policy perspectives on finding spaces in busy professional lives to engage in research and develop research-informed practice. It draws on notions of teachers as researchers, practitioner research and evidenc-ebased practice to argue that engagement in research is integral to teacher education and an empowering source of creative professional learning for teachers and teacher educators. Whilst acknowledging the challenges of this stance, examples from our own research practice illustrate how e-tools can assist us in building the capacity and confidence of staff and students in researching and enhancing teaching, learning and assessment practice. The second paper discusses IT skills development through the TEL pathway for trainee teachers in secondary education across different curriculum subjects. The lead tutor for the TEL pathway will use examples of activities developed with trainee teachers and university subject tutors to enhance their skills in using e-tools, such as QR codes, Kahoot, Padlet, Pinterest and cloud based learning. The paper will also focus on how these skills and tools can be used for action Discussant - the wider use of technologies in a university centre for teacher education; course management, recruitment and mentor training. research, evaluation and feedback and for marking and administrative tasks. The discussion will finish with thoughts on widening trainee teachers’ horizons into the future direction of educational technology. The third paper considers institutional policies and strategies for promoting and embedding TEL, including an initiative called ‘The Learning Conversation’, which aims ‘to share, highlight, celebrate, discuss, problematise, find things out...’ about TEL through an online space. The lead for ‘The Learning Conversation’ will offer reflections on this and other initiatives across the institution involving trainee teachers, university subject tutors, librarians and staff in student support services who are using TEL to engage, enthuse and support students on campus and during placements in schools. The fourth paper reflects on the use of TEL to engage with trainee teachers in post-compulsory education. This sector of education and training is more fragmented than primary and secondary schools sectors and so the challenges of building a community of practice that can support the development of innovative practice are greater.